Major Because hydroxyzine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including barbiturates. Moderate Barbiturates can cause CNS depression, and if used concomitantly with iloperidone, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. In theory, the use of barbiturates and iloperidone may also result in an increase in iloperidone elimination as a result of the CYP inducing effects of barbiturates.

Major Barbiturates induce CYP3A4 and may increase the metabolism of imatinib and decrease imatinib concentrations and clinical effects. Caution is recommended when imatinib is given in combination with barbiturates.

Major Barbiturates may increase the metabolism of indinavir and lead to decreased antiretroviral efficacy. In addition, indinavir may inhibit the CYP metabolism of barbiturates, resulting in increased barbiturate concentrations. Appropriate dose adjustments necessary to ensure optimum levels of both anti-retroviral agent and the barbiturate are unknown.

Anticonvulsant serum concentrations should be monitored closely if these agents are added; the patient should be observed for changes in the clinical efficacy of the antiretroviral or anticonvulsant regimen. Minor The risk of developing hypothermia is increased when methohexital is used with hypothermia-producing agents such as ethanol, insulins, phenothiazines, or other general anesthetics.

Major Both isoproterenol and general anesthetics sensitize myocardial tissue to the development of potentially life-threatening cardiac arrhythmias. Concomitant use of isoproterenol with general anesthetics can increase the risk of developing this adverse reaction. Major Because isradipine is a substrate of CYP3A4, the concomitant use of drugs that strongly induce CYP3A4, such as barbiturates, may cause a reduction in the bioavailability and thus decreased therapeutic effect of isradipine.

Consider alternative therapy; if co-use is necessary, patients should be monitored for potential loss of therapeutic effect when hepatic enzyme inducers are added to isradipine therapy. Major Use of barbiturates is not recommended for 2 weeks before or during itraconazole therapy.

Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of itraconazole. Monitor for breakthrough fungal infections. Major Avoid coadministration of ivabradine and barbiturates including primidone. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure. Major Ixabepilone is a CYP3A4 substrate and concomitant use with CYP3A4 inducers such as barbiturates may lead to reduced and subtherapeutic concentrations of ixabepilone.

Caution should be utilized when CYP3A4 inducers are coadministered with ixabepilone, and alternative therapies with low enzyme induction potential should be considered. Kava Kava, Piper methysticum: Major Any substances that act on the CNS, including barbiturates, may interact with kava kava.

Patients taking barbiturates should avoid use of this herb. Minor Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of ketoconazole. Clinicians should be alert for lack of efficacy of these antifungals in concurrent use. Drugs that are inducers of CYP3A4 activity, such as barbiturates, will decrease the plasma concentrations of lapatinib.

If treatment with one of these agents is necessary, consider a lapatinib dose escalation. If a strong CYP3A4 inducer is discontinued, reduce the lapatinib dose to the indicated dose. Moderate Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy.

Minor Limited data suggest that leucovorin and levoleucovorin may interfere with the activity of anticonvulsants such as barbiturates. Folic acid can decrease serum concentrations of anticonvulsants in children.

Leucovorin shares metabolic pathways with folic acid. Clinicians should consider careful monitoring of patients. Minor Barbiturates may induce the metabolism of levobupivacaine resulting in a decreased serum half-life. Dosage adjustments of levobupivacaine may be necessary.

If a barbiturate is initiated a patient taking an opioid agonist, use a lower initial dose of the barbiturate and titrate to clinical response. Major Inhalational general anesthetics may sensitize the myocardium to the effects of lisdexamfetamine. Moderate Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics. Moderate Monitor for additive sedation during coadministration of lofexidine and barbiturates.

Lofexidine can potentiate the effects of CNS depressants such as barbiturates. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known.

The use of barbiturates parenterally may cause vasodilation and an additive risk for hypotension and may lead to bradycardia and syncope; in these patients, careful monitoring of blood pressure should occur. Major Barbiturates may increase the metabolism of lopinavir and lead to decreased antiretroviral efficacy.

In addition, coadministration of lopinavir boosted with ritonavir may induce the CYP metabolism of barbiturates, resulting in decreased barbiturate concentrations.

Appropriate dose adjustments necessary to ensure optimum levels of both anti-retroviral agent and the barbiturate are unknown; however, once daily lopinavir; ritonavir should not be used. Monitor for potential reduced cholesterol-lowering efficacy when barbiturates are co-administered with HMG-CoA reductase inhibitors metabolized by CYP3A4 including lovastatin.

Moderate Loxapine can potentiate the actions of other CNS depressants, such as barbiturates. Severe Concurrent use of lurasidone with strong CYP3A4 inducers, such as barbiturates, is contraindicated.

Lurasidone is primarily metabolized by CYP3A4. Decreased blood concentrations of lurasidone are expected when the drug is co-administered with strong inducers of CYP3A4. Minor Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as barbiturates. Caution should be exercised when using these agents concurrently.

Moderate Barbiturates induce hepatic microsomal enzymes and may increase the metabolism of mebendazole if given concomitantly. This effect can cause decreased levels of plasma mebendazole but is probably important only in the treatment of extraintestinal infections, such as hydatid cyst disease, and not in the treatment of intestinal helminths.

Moderate Additive CNS depression may occur if barbiturates are used concomitantly with meclizine. Moderate The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria.

Coadministration of mefloquine and anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Major Use caution when combining melatonin with other traditional sedatives and hypnotics, including the sedative barbiturates.

Use of more than one agent for hypnotic purposes may increase the risk for over-sedation, CNS effects, or sleep-related behaviors. If a barbiturate is taken for seizure control, watch for changes in anticonvulsant activity. Be alert for unusual changes in moods or behaviors. Patients reporting unusual sleep-related behaviors likely should discontinue melatonin use.

Additionally, melatonin exposure and efficacy may be reduced when combined with barbiturates such as phenobarbital, as barbiturates induce many CYP isoenzymes, including CYP1A2, the primary metabolic pathway for melatonin.

If meperidine is initiated in a patient taking a barbiturate, reduce initial dosage and titrate to clinical response. Additionally, concurrent use of meperidine with barbiturates may decrease meperidine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists.

Barbiturates are inducers of CYP3A4, an isoenzyme partially responsible for the metabolism of meperidine. Major Additive CNS depression may occur if barbiturates are used concomitantly with other anxiolytics, sedatives, and hypnotics like meprobamate. Caution should be exercised during concomitant use of anxiolytics, sedatives, and hypnotics and any barbiturate; dosage reduction of one or both agents may be necessary.

Major Coadministration of barbiturates and repaglinide may decrease the serum concentration of repaglinide; if coadministration is necessary, a dose increase of repaglinide may be necessary and increased frequency of blood glucose monitoring.

Monitor for the possibility of reduced effectiveness of repaglinide and possible symptoms indicating hyperglycemia. In patients treated with methadone for opioid use disorder, cessation of other CNS depressants is preferred in most cases.

Additionally, concurrent use of methadone with barbiturates may decrease methadone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. Minor Methazolamide can induce osteomalacia in patients treated chronically with barbiturates.

Methazolamide can also increase the rate of excretion of weakly acidic drugs, such as barbiturates. Dosage reduction of one or both agents may be necessary. Moderate CNS depression can be increased when methscopolamine is combined with other CNS depressants such as any anxiolytics, sedatives, and hypnotics. Moderate Barbiturates induce hepatic microsomal enzymes and may increase the hepatic metabolism of succinimides. This may lead to a decrease in succinimide plasma concentration and a reduction in half-life.

Minor Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation. Other drugs that may also cause drowsiness, such as barbiturates, should be used with caution. Moderate The concomitant administration of metyrosine with barbiturates can result in additive sedative effects. Moderate While other hepatic enzyme inducers have been shown to accelerate the metabolism of mexiletine, no data are available regarding the effects of barbiturates on mexiletine.

An interaction between barbiturates and mexiletine, however, may be possible. Additionally, barbiturates may increase the metabolism of midazolam. Midazolam is a CYP3A4 substrate. Minor Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as barbiturates.

Moderate Mitotane can cause sedation, lethargy, vertigo, and other CNS side effects. Mitotane should be used cautiously with other drugs that may cause CNS depression including barbiturates.

Major It is not clear how modafinil interacts with barbiturates like phenobarbital. Modafinil is partially metabolized by CYP3A4 and combined use with CYP3A4 inducers such as phenobarbital and other barbiturates may result in decreased modafinil efficacy.

Barbiturates used for sleep could counteract the effect of modafinil on wakefulness, and would not ordinarily be prescribed. The potential effects of combining modafinil with anticonvulsant barbiturate medications are unclear. Many psychostimulants can reduce the seizure threshold, but it is not clear if modafinil can affect seizure control. Severe Patients receiving monoamine oxidase inhibitors MAOIs may have an increased risk of hypotension after administration of general anesthetics, although specific studies are not available.

Combined hypotensive effects are also possible with the combined use of MAOIs and spinal anesthetics. In general, MAOIs should be discontinued for at least 10 days prior to elective surgery.

Although no dosage adjustment is recommended, it is reasonable to closely monitor a patient when potent cytochrome P enzyme inducers, such as barbiturates, are coadministered with montelukast.

Be alert for decreased clinical response to montelukast. If morphine is initiated in a patient taking a barbiturate, reduced initial dosages are recommended. For extended-release tablets, start with the lowest possible dose of morphine i. If a barbiturate is prescribed for a patient taking an opiate agonist, use a lower initial dose of the barbiturate and titrate to clinical response.

Moderate Concomitant use of nabilone with other CNS depressants, like barbiturates, can potentiate the effects of nabilone on respiratory depression.

Moderate Additive CNS depression may occur if barbiturates are used concomitantly with nalbuphine. Caution should be exercised during concomitant use of nalbuphine and any barbiturate. Major Coadministration with phenobarbital and, potentially, other barbiturates may increase the metabolism of nelfinavir and lead to decreased nelfinavir concentrations resulting in reduction of antiretroviral efficacy and development of viral resistance.

If nelfinavir and barbiturates are used together, the patient must be closely monitored for antiviral efficacy. Major Avoid concomitant use of methohexital with neratinib due to decreased efficacy of neratinib.

Because of the significant impact on neratinib exposure from strong CYP3A4 induction, the potential impact on neratinib efficacy from concomitant use with moderate CYP3A4 inducers should be considered as they may also significantly decrease neratinib exposure.

Major The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics. Moderate Coadministration of nevirapine with barbiturates, which induce the activity of CYP3A, would be expected to increase the clearance of nevirapine, thereby decreasing nevirapine plasma concentrations.

However, since nevirapine also induces CYP3A enzymes, decreases in anticonvulsant serum concentrations may be noted with the possibility of new seizure activity. The appropriate drug-dose adjustments necessary to ensure optimum levels of both antiretroviral drugs and barbiturates are unknown.

Major Patients should be monitored for loss of antihypertensive effect if CYP3A4 enzyme inducers like the barbiturates are added to nicardipine therapy. Rifampin is a potent hepatic enzyme inducer and has been shown to exert a substantial reduction of the oral bioavailability of some calcium channel blockers.

This interaction should be considered with other potent CYP3A4 inhibitors including the barbiturates. Major Avoid coadministration of nifedipine with barbiturates and consider alternative therapy if possible. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers warn avoidance of such inducers. Major In epileptic patients taking phenobarbital with or without other enzyme-inducing anticonvulsants, there is a 7-fold decrease in the AUC of nimodipine due to hepatic enzyme induction.

Patients receiving barbiturates and nimodipine concomitantly should be monitored closely for efficacy. Although no data are available, it is likely that nimodipine, a CYP3A4 substrate, may be affected by the coadministration of all barbiturates.

Major Avoid the use of barbiturates with nintedanib, as these drugs are expected to decrease the exposure of nintedanib and compromise its efficacy. Major Coadministration of nisoldipine with CYP3A4 inducers like the barbiturates should be avoided and alternative antihypertensive therapy should be considered.

Coadministration of a strong CYP3A4 inducer with nisoldipine in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Major Norepinephrine interacts with general anesthetics because the anesthetics increase cardiac irritability, which can lead to arrhythmias. Major Avoid the coadministration of olaparib with methohexital due to decreased olaparib exposure; if concomitant use is unavoidable, there is a potential for decreased efficacy of olaparib.

Minor Ondansetron elimination may be affected by cytochrome P inducers. In a pharmacokinetic study of 16 patients with epilepsy who were maintained chronically on CYP3A4 inducers e. However, these changes in ondansetron exposure are not thought to be clinically relevant; no dosage adjustment for ondansetron is recommended when CYP inducers are used concurrently.

Moderate Additive CNS depression may occur when oxybutynin is used concomitantly with other CNS-depressant drugs, including anxiolytics, sedatives, and hypnotics. In addition, because oxybutynin is metabolized by CYP3A4, administration with drugs that induce CYP3A4 such as barbiturates may reduce the serum concentration and effects of oxybutynin. Patients receiving these drugs concomitantly should be monitored for reduced efficacy. If oxymorphone is initiated in a patient taking a barbiturate, use an initial dose of immediate-release oxymorphone at one-third to one-half the usual dosage and titrate to clinical response.

If the extended-release oxymorphone tablets are used concurrently with a barbiturate, use a lower initial dose of extended-release oxycodone and titrate to clincal response.

If a barbiturate is prescribed for a patient taking an opioid agonist, use a lower initial dose of the barbiturate and titrate to clinical response.

Major Adverse cardiovascular effects can develop as a result of concomitant administration of oxytocin with general anesthetics. Minor Paclitaxel is metabolized by hepatic cytochrome P isoenzymes 2C8 and 3A4. Major Avoid using a strong inducer of CYP3A4 if possible during the 1-month injectable dosing interval of Invega Sustenna or the 3-month injectable dosing interval of Invega Trinza.

If use of a strong CYP3A4 inducer such as a barbiturate is required in patients receiving injectable paliperidone, consider management with oral paliperidone. A dosage increase of oral paliperidone may be required during coadministration of a strong inducer of both CYP3A4 and P-gp.

However, concurrent use of oral paliperidone with a strong CYP3A4 inducer alone may not be clinically relevant since this isoenzyme contributes to only a small fraction of total body clearance of the drug. It should be noted that clinically significant barbiturate enzyme-induction occurs after several days and may not be clinically significant with short-term use of barbiturates.

Moderate Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation. Moderate Barbiturates may induce various hepatic CYP isoenzymes, including those responsible for the metabolism of paroxetine. Clinicians should be aware of the potential for reduced SSRI efficacy with concurrent administration of a barbiturate, especially in chronic use. Moderate Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the barbiturates.

Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Phenothiazines can also lower the seizure threshold, which may be important in patients taking a barbiturate for the treatment of seizures.

Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with the use of sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.

Barbiturates may cause additive sedation or other CNS depressive effects when used concurrently with topiramate. When topiramate is combined with phentermine for the treatment of obesity, a greater risk of CNS depression exists.

Concurrent use of topiramate and drugs that cause thrombocytopenia, such as the barbiturates, may also increase the risk of bleeding; monitor patients appropriately. An increase in dose of pimavanserin may be required during concurrent use with strong CYP3A4 inducers such as barbiturates and primidone. Moderate General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.

Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction. Moderate Use pomalidomide and barbiturates together with caution; decreased pomalidomide exposure may occur resulting in reduced pomalidomide effectiveness. Major The action of barbiturates is potentiated by the acetylcholinesterase inhibitors, which should be considered when using pralidoxime.

Barbiturates should be used with caution to treat convulsions produced by acetylcholinesterase inhibitors. Major The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction. Severe The concomitant use of barbiturates, such as phenobarbital, with praziquantel is contraindicated due to decreased exposure and efficacy of praziquantel.

Barbiturates are strong CYP3A4 inducers and praziquantel is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of praziquantel. In a crossover study with a 2-week washout period, administration of praziquantel followed by another strong CYP3A inducer, rifampin, resulted in undetectable plasma concentrations of praziquantel in 7 out of 10 subjects. Moderate Concomitant administration of pregabalin with CNS-depressant drugs, including barbiturates, can potentiate the CNS effects of either agent.

Pregabalin can cause considerable somnolence and the combined use of ethanol or other CNS depressants with pregabalin may lead to an additive drowsy effect. Major If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Moderate Use procarbazine and barbiturates together with caution; additive CNS depression may occur. Barbiturates induce hepatic enzymes and can accelerate the rate of metabolism of hormones, including progestins.

For patients on hormone replacement treatments HRT with progestins, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy.

For women taking hormonal contraception for birth control, loss of efficacy may lead to breakthrough bleeding and an increased risk for pregnancy. Pregnancy has been reported during therapy with hormonal contraceptives in patients receiving barbiturates.

If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed hepatic enzyme inducing drugs. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of the interacting medication. Additionally, epileptic women taking both anticonvulsants and OCs may be at higher risk of folate deficiency secondary to additive effects on folate metabolism; these women should ensure adequate folate supplementation.

Additionally, barbiturates may increase the metabolism of quazepam. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration 7 to 14 days of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.

Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. Major Quinine may interfere with the hepatic metabolism of phenobarbital or other barbiturates, resulting in higher plasma concentrations of the barbiturate.

It ain't that easy. Later when wine coolers came onto the market, they substituted for beer. Due to the heat and expanse of the Houston area residents spent long drives in their cars, "the music that most appropriately complements that has always been the music of DJ Screw, it's slowed down — and when I say slowed down I mean he would record sessions in his apartment with rappers freestyling over beats and he would make these big mixtapes and then he would actually slow them down even further on his cassette recorder.

Respiratory depression is a potentially serious or fatal adverse drug reaction associated with the use of codeine , but mainly the danger lies in the much more potent and CNS - depressing phenothiazine-related antihistamine promethazine. This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose: As with most CNS depressants, mixing with alcohol greatly increases the risk of respiratory failure and other complications.

Ed Winter, assistant chief of the Coroner's Office, said the levels of the medication were elevated, but not enough to deem the death an overdose. However, Pimp C had a history of sleep apnea , a condition that causes one to stop breathing for short periods during sleep.

Vicodin, Percocet, Morphine, etc. Oral Methadone is very different than IV Methadone. Oral Methadone is partially stored in the liver for late use. IV Methadone acts more like heroin. In most states you must go to a pain clinic or a Methadone maintenance clinic to be prescribed Methadone.

Methadone is a long acting pain reliever producing effects that last from twelve to forth-eight hours. Ideally, Methadone frees the client from the pressures of obtaining illegal heroin, from the dangers of injection and from the emotional roller coaster that most opiates produce.

Methadone, if taken for long periods and at large doses, can lead to a very long withdrawal period. The withdrawals from Methadone are more prolonged and troublesome than those provoked by heroin cessation, yet the substitution and phased removal of methadone is an acceptable method of detoxification for patients and therapists.

Methamphetamine is closely related chemically to amphetamine, but the central nervous system effects of Methamphetamine are greater. Methamphetamine is made in illegal laboratories and has a high potential for abuse and dependence. The drug can be taken orally, injected, or inhaled. Acute higher does lead to enhanced stimulation of the central nervous system and induce euphoria, alertness, reduced appetite, and a sense of increased energy and power. Cardiovascular responses to Methamphetamine include increased blood pressure and cardiac arrhythmias.

More acute responses produce anxiety, paranoia, hallucinations, psychotic behavior, and eventually, depression and exhaustion.

The effects of Methamphetamine generally last hours and the drug has a half-life of hours in the body. Methamphetamine is excreted in the urine primarily as amphetamine and oxidized and deaminated derivatives. Thus, the presence of the parent compound in the urine indicates Methamphetamine use. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.

Moderate CYP enzyme inhibitors, like clarithromycin, may inhibit the hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP inhibitors are coadministered with doxercalciferol.

Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Clarithromycin has a possible risk of causing QT prolongation and torsades de pointes TdP. Avoid coadministration of clarithromycin and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.

Major Use caution if coadministration of dronabinol with clarithromycin is necessary, and monitor for an increase in dronabinol-related adverse reactions e.

Concomitant use may result in elevated plasma concentrations of dronabinol. Severe Concomitant use of dronedarone with clarithromycin is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of mg twice daily the FDA-approved dose and up to 25 milliseconds at doses of mg twice daily.

Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.

Major Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes TdP. Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include clarithromycin. Major Plasma concentrations of tamsulosin may be increased with concomitant use of clarithromycin.

Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as clarithromycin, should be avoided.

No dosage adjustment is required in patients with atrial fibrillation. Edoxaban is a P-glycoprotein P-gp substrate and clarithromycin is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of clarithromycin; monitor for increased adverse effects of edoxaban. Major The manufacturer of efavirenz recommends that alternatives to clarithromycin be considered when a macrolide antibiotic is required in patients receiving efavirenz.

Coadministration of efavirenz and clarithromycin may increase the risk for QT prolongation and torsade de pointes TdP. QT prolongation has also been observed with use of efavirenz. In addition, concurrent use of efavirenz with clarithromycin mg PO every 12 hours for seven days resulted in a significant decrease in the serum concentration of clarithromycin, but the clinical significance of this is not known.

Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: Severe Concomitant use of elagolix and strong organic anion transporting polypeptide OATP 1B1 inhibitors such as clarithromycin is contraindicated. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to clarithromycin in a patient receiving elagolix. Major Concurrent administration of elbasvir with clarithromycin should be avoided if possible; consider use of azithromycin in place of clarithromycin.

Use of these drugs together is expected to significantly increase the plasma concentration of elbasvir, and may result in adverse effects i. Major Concurrent administration of grazoprevir with clarithromycin should be avoided if possible; consider use of azithromycin in place of clarithromycin.

Use of these drugs together is expected to significantly increase the plasma concentration of grazoprevir, and may result in adverse effects i. Severe Eletriptan is contraindicated with recent use i.

The coadministration of eliglustat with both clarithromycin and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and clarithromycin can independently prolong the QT interval, and coadministration increases this risk. Coadministration of eliglustat with CYP3A inhibitors such as clarithromycin increases eliglustat exposure and the risk of serious adverse events e. Emtricitabine; Rilpivirine; Tenofovir alafenamide: Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: Emtricitabine; Tenofovir disoproxil fumarate: Major Avoid coadministration of encorafenib and clarithromycin due to increased encorafenib exposure and QT prolongation.

If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of clarithromycin. If clarithromycin is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of clarithromycin.

Coadministration of a strong CYP3A4 inhibitor with a single 50 mg dose of encorafenib 0. Major Coadministration of enzalutamide and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction; consider alternatives to clarithromycin if treatment with enzalutamide is necessary.

Major Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering clarithromycin with epirubicin. Acute cardiotoxicity can also occur during administration of epirubicin; although, the incidence is rare. Severe Coadministration of clarithromycin and eplerenone is contraindicated.

Clarithromycin potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension. Severe The concurrent use of certain macrolides clarithromycin, erythromycin, and troleandomycin with ergot alkaloids is thus generally considered contraindicated.

The simultaneous use of some ergot alkaloids with troleandomycin has produced ergot toxicity e. The mechanism is related to inhibition of ergot metabolism via CYP3A4. Major Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.

Drugs with a possible risk for QT prolongation and torsades de pointes TdP that should be used cautiously with eribulin include clarithromycin. Major Avoid coadministration of erlotinib with clarithromycin if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements.

Major Both clarithromycin and erythromycin are macrolide antibiotics and coadministration would represent duplicate therapy. Both drugs have been associated with QT prolongation and TdP. Major Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes TdP , such as clarithromycin, should be done with caution and close monitoring.

In addition, escitalopram is metabolized by CYP3A4. Theoretically, clarithromycin may inhibit this enzyme and lead to elevated plasma levels of this SSRI. However, because escitalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease its clearance.

Major Coadministration of eslicarbazepine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. Moderate Clarithromycin is a CYP3A4 inhibitor and may reduce the metabolism of estazolam and increase the potential for benzodiazepine toxicity. CYP3A4 is a primary metabolic pathway for eszopiclone, and increased systemic exposure to eszopiclone increases the risk of next-day psychomotor or memory impairment, which may decrease the ability to perform tasks requiring full mental alertness such as driving.

Although other macrolide antibiotics, such as erythromycin, inhibit CYP3A4 to a lesser extent than clarithromycin, a clinically relevant interaction is possible, and dose adjustments of eszopiclone may be necessary. Minor Coadministration of etonogestrel and strong CYP3A4 inhibitors such as clarithromycin may increase the serum concentration of etonogestrel.

Major Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with clarithromycin. Coadministration may cause accumulation of etoposide and decreased metabolism, resulting in increased etoposide concentrations. Major Coadministration of etravirine and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction.

Major Avoid coadministration of clarithromycin with everolimus Afinitor; Afinitor Disperz due to increased plasma concentrations of everolimus. Coadministration of clarithromycin with everolimus Zortress is not recommended without close monitoring of everolimus whole blood trough concentrations.

Severe The concurrent use of clarithromycin and simvastatin is contraindicated due to the risk of myopathy and rhabdomyolysis. If no alternative to a short course of clarithromycin therapy is available, simvastatin use must be suspended during clarithromycin treatment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with clarithromycin include ezogabine.

Major Coadministration of felbamate and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. Moderate Fentanyl is metabolized by the cytochrome P 3A4 isoenzyme.

Moderate Fesoterodine is rapidly hydrolyzed to its active metabolite, 5-hydroxymethyltolterodine, which is metabolized via hepatic CYP3A4. In theory, the potent CYP3A4 inhibitory effects of clarithromycin may result in an increase in plasma concentrations of 5-hydroxymethyltolterodine. Major Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes TdP.

Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fingolimod include clarithromycin. Major Due to an increased risk for QT prolongation and torsade de pointes TdP , caution is advised when administering clarithromycin with flecainide.

Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Severe The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as clarithromycin, is contraindicated.

Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.

Severe Coadministration is contraindicated. Fluconazole has been associated with QT prolongation and clarithromycin has been specifically established to have a causal association with QT prolongation and torsade de pointes TdP. The changes appeared to be of minor consequence in healthy subjects. The potential for a more significant interaction between fluconazole and clarithromycin might exist at higher dosages of either drug; caution is advised in such circumstances but should not normally alter therapy.

Fluconazole is usually considered a less potent inhibitor of CYP3A4 than other azole-family systemic antifungal agents e. Azithromycin can be considered as an alternative macrolide antimicrobial if appropriate for the clinical circumstance, due to its lack of metabolism via CYP3A4. Major Because QT prolongation and torsade de pointes TdP have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval.

Drugs with a possible risk for QT prolongation and TdP include clarithromycin. Major Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering clarithromycin with olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.

Additionally, clarithromycin is associated with an established risk for QT prolongation and TdP. Minor Due to the potential for QT prolongation and torsade de pointes TdP , caution is advised when administering clarithromycin with fluphenazine.

Clarithromycin is associated with an established risk for QT prolongation and TdP, while fluphenazine a phenothiazine is associated with a possible risk for QT prolongation. Moderate Clarithromycin is a CYP3A4 inhibitor and may reduce the metabolism of flurazepam and increase the potential for benzodiazepine toxicity. Moderate Rare reports of rhabdomyolysis have been reported in patients taking clarithromycin and fluvastatin.

Major There may be an increased risk for QT prolongation and torsade de pointes TdP during concurrent use of fluvoxamine and clarithromycin. Clarithromycin is associated with an established risk for QT prolongation and TdP while QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Moderate The incidence of marijuana associated adverse effects may change following coadministration with clarithromycin. Clarithromycin is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, deltatetrahydrocannabinol DeltaTHC.

When given concurrently with clarithromycin, the amount of DeltaTHC converted to the active metabolite hydroxy-deltatetrahydrocannabinol OH-THC may be reduced. Moderate Concomitant administration of clarithromycin and mometasone may increase systemic exposure to mometasone, increasing the risk of corticosteroid-related adverse events.

Exercise caution when administering mometasone with clarithromycin long-term and monitor closely for hypercorticism and adrenal suppression. Minor Clarithromycin is a CYP3A4 inhibitor and may decrease the clearance of fosamprenavir leading to increased serum concentrations. Major When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as clarithromycin.

Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes TdP. Clarithromycin is also associated with an established risk for QT prolongation and TdP. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. Major Coadministration of fosphenytoin and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction.

Alternatives to clarithromycin should be considered in patients who are taking potent CYP3A4 inducers. Additionally, there have been postmarketing reports of interactions of clarithromycin and phenytoin, which may also occur with fosphenytoin.

The clarithromycin manufacturer recommends caution if coadministered. Moderate Monitor for fostamatinib toxicities that may require fostamatinib dose reduction i. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R, which may increase the risk of adverse reactions.

Moderate Galantamine is a primary substrate for CYP3A4 and the bioavailability of galantamine may be increased when coadministered with potent inhibitors of CYP3A4 such as clarithromycin.

Monitor for galantamine-related adverse effects such as nausea, vomiting, loss of appetite, diarrhea, headache, confusion, and excessive sweating.

Major Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and clarithromycin are used concomitantly.

Gefitinib is metabolized significantly by CYP3A4 and clarithromycin is a strong CYP3A4 inhibitor; coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations.

Major Due to an increased risk for QT prolongation and torsade de pointes TdP , caution is advised when administering clarithromycin with gemifloxacin. Gemifloxacin may also prolong the QT interval in some patients.

The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher Gemtuzumab Ozogamicin: Major Use gemtuzumab ozogamicin and clarithromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes TdP.

If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin.

Moderate Caution is advised with the coadministration of glecaprevir and clarithromycin as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects.

Moderate Caution is advised with the coadministration of pibrentasvir and clarithromycin as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein P-gp ; clarithromycin is an inhibitor of P-gp. Major Clarithromycin should be used cautiously and with close monitoring with goserelin. Androgen deprivation therapy e. Major Due to an increased risk for QT prolongation and torsade de pointes TdP , caution is advised when administering clarithromycin with granisetron.

Both granisetron and clarithromycin are associated with prolongation of the QT interval, and clarithromycin has also been associated with an established risk for TdP. Minor Grapefruit juice has been reported to decrease the metabolism of drugs metabolized via cytochrome CYP 3A4 isozyme. In a randomized crossover study in healthy volunteers, grapefruit juice did not have a significant affect on the bioavailability of clarithromycin nor did it affect the metabolism of clarithromycin to its active metabolite.

Major Clarithromycin may significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release ER guanfacine recommends that, if these agents are taken together, the guanfacine dosage should be decreased to half of the recommended dose.

Specific recommendations for immediate-release IR guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. If clarithromycin is discontinued, the guanfacine ER dosage should be increased back to the recommended dose.

Severe Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes and should be avoided in combination with other agents known to cause QT prolongation, such as clarithromycin. Major Concurrent use of clarithromycin and haloperidol should be avoided if possible. QT prolongation and torsade de pointes TdP have been observed during haloperidol treatment.

Excessive doses particularly in the overdose setting of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Because clarithromycin is also associated with an increased risk for QT prolongation and TdP, the need to coadminister clarithromycin with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits.

Clarithromycin is an inhibitor of CYP3A4. Major Consider periodic monitoring of EGCs for QT prolongation and monitor electrolytes if coadministration of histrelin and clarithromycin is necessary; correct any electrolyte abnormalities.

Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Moderate Clarithromycin inhibits CYP3A4 and has the potential to result in increased plasma concentrations of corticosteroids. Therefore, the dose of corticosteroid should be titrated to avoid steroid toxicity. Major Avoid coadministration of hydroxychloroquine and clarithromycin.

Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes TdP have been reported with the use of hydroxychloroquine.

The metabolism of progesterone is inhibited by ketoconazole, a known inhibitor of cytochrome P 3A4 hepatic enzymes. Theoretically, the metabolism of hydroxyprogesterone may also be inhibited by ketoconazole. It has not been determined whether other drugs which inhibit CYP3A4 hepatic enzymes would have a similar effect. Other such drugs include cimetidine, clarithromycin, danazol, diltiazem, erythromycin, fluconazole, itraconazole, troleandomycin, verapamil, and voriconazole.

This list is not inclusive of all drugs that inhibit CYP3A4. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include clarithromycin. Major Avoid the concomitant use of ibrutinib and clarithromycin; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity e. If short-term use of clarithromycin is necessary e. Resume ibrutinib at the previous dose when clarithromycin is discontinued.

When ibrutinib was administered with multiple doses of other strong CYP3A4 inhibitors, the Cmax and AUC values of ibrutinib were increased significantly. Major Ibutilide administration can cause QT prolongation and torsades de pointes TdP ; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Major Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes TdP and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin.

Major Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clarithromycin, a CYP3A substrate, as clarithromycin toxicities may be significantly increased. Major The concomitant use of ifosfamide, a CYP3A4 substrate, and clarithromycin, a strong CYP3A4 inhibitor and substrate, may decrease the metabolism of ifosfamide to its active metabolite, 4-hydroxy-ifosfamide.

As a result of this interaction, ifosfamide treatment effectiveness may be reduced. Major Avoid coadministration of iloperidone and clarithromycin due to the potential for QT prolongation; iloperidone exposure may also increase. If coadministration cannot be avoided, decrease the iloperidone dose by one-half. Resume the prior iloperidone dose if clarithromycin is discontinued. Minor Clarithromycin is a significant inhibitor of CYP3A4 isoenzymes and should be used cautiously with CYP3A4 substrates, such as imatinib, due to the potential for reduced metabolism and drug accumulation.

Patients with impaired renal function may require a reduced dosage of clarithromycin. Major Avoid coadministration of inotuzumab ozogamicin with clarithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes TdP. If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment.

Inotuzumab has been associated with QT interval prolongation. Moderate The concomitant use of clarithromycin and insulin or other antidiabetic agents can result in significant hypoglycemia. Major Avoid administration of clarithromycin during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Concomitant use may increase systemic exposure of irinotecan. Moderate Concomitant use of isavuconazonium with clarithromycin may result in increased serum concentrations of both drugs.

Clarithromycin is a substrate and moderate inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4.

Medsafe: New Zealand Medicines and Medical Devices Safety Authority

Following administration of droperidol, lower doses of the other CNS depressant should be used. Rifampin is a potent hepatic enzyme inducer and has been shown brompheniramine exert a substantial reduction of the oral bioavailability of some calcium codeine blockers. Major Close clinical monitoring is advised when administering clarithromycin with rilpivirine due brompheniramine an increased codeine for rilpivirine-related adverse withs. A retrospective, case codeine study, found the risk of hospitalization due to hypotension or shock to be significantly increased in geriatric patients exposed to clarithromycin during codeine calcium-channel blocker therapy OR 3, codeine with brompheniramine. Clarithromycin is an inhibitor of CYP3A4. Drugs which increase the activity of this enzyme, such as barbiturates should not be used with hemin. It brompheniramine likely that other barbiturates, like methohexital, codeine with brompheniramine, would be affected similarly by valproic acid. Major Coadministration of bosentan and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. Gefitinib is metabolized significantly by CYP3A4 and clarithromycin is a strong CYP3A4 codeine coadministration may with the metabolism of gefitinib and increase gefitinib concentrations. Alternatives to clarithromycin brompheniramine be considered in patients who are taking prozac online united states. Treatment with clozapine has been associated with QT prolongation, TdP, codeine with brompheniramine, cardiac arrest, and sudden death. These agents may include clarithromycin. Patients should be monitored for an exaggerated with effect brompheniramine valproic acid is used concomitantly. Moderate Chloramphenicol inhibits the cytochrome P enzyme system and can affect the hepatic metabolism of phenobarbital, codeine with brompheniramine.

Codeine

Brompheniramine

Careful monitoring of glucose is brompheniramine. Minor Barbiturates induce hepatic CYP enzymes including 3A4, 2C19 and 2C9 and may reduce effective serum concentrations of ketoconazole. An enhanced with of the displaced drug may occur. Major Coadministration of dexamethasone and clarithromycin may codeine clarithromycin serum concentrations due to CYP3A4 enzyme induction. Buprenorphine doses may need brompheniramine be increased if any of these agents are added. In addition, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Caution should be exercised during with use of skeletal muscle relaxants and barbiturates; dosage reduction of one or both agents may be necessary. Major Do not exceed 40 mg per day of pravastatin if coadministration with clarithromycin cannot be avoided. Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Careful monitoring of blood glucose is recommended. Increased eplerenone concentrations may lead to a codeine of developing hyperkalemia and hypotension, codeine with brompheniramine.

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