In addition, abuse of opioids can occur in the absence of true addiction. Promethazine VC with Codeine Oral Solution, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. The risk is increased with concurrent use of Promethazine VC with Codeine Oral Solution with alcohol and other central nervous system depressants [see Warnings and Precautions 5.
Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
Dependence Psychological dependence, physical dependence, and tolerance may develop upon repeated administration of opioids; therefore, Promethazine VC with Codeine Oral Solution should be prescribed and administered for the shortest duration that is consistent with individual patient treatment goals and patients should be reevaluated prior to refills [see Dosage and Administration 2. Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued oral opioid use, although some mild degree of physical dependence may develop after a few days of opioid therapy.
If Promethazine VC with Codeine Oral Solution is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur.
Some or all of the following can characterize this syndrome: Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations 8. Codeine may cause miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic eg, pontine lesions of hemorrhagic or ischemic origin may produce similar findings.
Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology Promethazine Signs and symptoms of overdosage with promethazine range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness and sudden death.
Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis and extensor-plantar reflexes Babinski reflex. Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur. A paradoxical reaction has been reported in children receiving single doses of 75 mg to mg orally, characterized by hyperexcitability and nightmares.
Atropine-like signs and symptoms dry mouth, fixed dilated pupils, flushing, tachycardia, hallucinations, gastrointestinal symptoms, convulsions, urinary retention, cardiac arrhythmias and coma may be observed. Impaired secretion from sweat glands following toxic doses of drugs with anticholinergic side effects may predispose to hyperthermia. Phenylephrine Signs and symptoms of overdosage with phenylephrine include headache, vomiting, hypertension, reflex bradycardia, cardiac arrhythmias including ventricular premature beats and ventricular tachycardia, convulsions, and cerebral hemorrhage.
Overdosage may also be associated with a sensation of fullness in the head and tingling of the extremities. Headache may be a symptom of hypertension. Bradycardia may be seen early in phenylephrine overdosage through stimulation of baroreceptors.
Treatment of Overdose Treatment of overdosage is driven by the overall clinical presentation, and consists of discontinuation of Promethazine VC with Codeine Oral Solution together with institution of appropriate therapy. Give primary attention to the reestablishment of adequate respiratory exchange through provision of a patent and protected airway and the institution of assisted or controlled ventilation.
Employ other supportive measures including oxygen and vasopressors in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. Gastric emptying may be useful in removing unabsorbed drug. The opioid antagonists, naloxone and nalmefene, are specific antidotes for respiratory depression resulting from opioid overdose.
For clinically significant respiratory or circulatory depression secondary to codeine overdose, administer an opioid antagonist. An antagonist should not be administered in the absence of clinically significant respiratory depression.
Because the duration of opioid reversal is expected to be less than the duration of action of codeine in Promethazine VC with Codeine Oral Solution, carefully monitor the patient until spontaneous respiration is reliably reestablished. The respiratory depressant effects of promethazine are not reversed by opioid antagonists, such as naloxone. Hemodialysis is not routinely used to enhance the elimination of codeine or promethazine from the body. Adrenergic receptor blocking agents beta-blockers , such as propranolol, may be used for the treatment of cardiac toxicity due to phenylephrine.
Promethazine VC with Codeine Description Promethazine VC with Codeine Oral Solution promethazine hydrochloride, phenylephrine hydrochloride, and codeine phosphate oral solution contains codeine an opioid agonist; promethazine, a phenothiazine; and phenylephrine, an alpha-1 adrenergic receptor agonist.
Codeine is one of the naturally occurring phenanthrene alkaloids of opium derived from the opium poppy, it is classified pharmacologically as a narcotic analgesic. The phosphate salt of codeine occurs as white, needle-shaped crystals or white crystalline powder.
Codeine phosphate is freely soluble in water and slightly soluble in alcohol. The molecular weight is Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder which slowly oxidizes and turns blue on prolonged exposure to air. It is soluble in water and freely soluble in alcohol.
It occurs as white or nearly white crystals, having a bitter taste. It is freely soluble in water and alcohol. Phenylephrine hydrochloride is subject to oxidation and must be protected from light and air. Promethazine VC with Codeine - Clinical Pharmacology Mechanism of Action Codeine Codeine is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine.
The analgesic and antitussive properties of codeine have been speculated to come from its conversion to morphine. The precise mechanism of action of codeine and other opiates is not known; however, codeine is believed to act centrally on the cough center.
In excessive doses, codeine will depress respiration. Promethazine Promethazine is a phenothiazine derivative, which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution. Promethazine possesses antihistamine H1 receptor antagonist , antiemetic, sedative, and anticholinergic effects.
It prevents released histamine from dilating capillaries and causing edema of the respiratory mucosa. Phenylephrine Phenylephrine is a sympathomimetic amine that exerts a decongestant action on the nasal mucosa via alpha adrenergic receptor activity. It has the potential for excitatory side effects. Pharmacodynamics Codeine Effects on the Central Nervous System Codeine produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and to electrical stimulation.
Codeine causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic eg, pontine lesions of hemorrhagic or ischemic origins may produce similar findings. Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Effects on the Gastrointestinal Tract and Other Smooth Muscle Codeine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum.
Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation.
Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase. Effects on the Cardiovascular System Codeine produces peripheral vasodilation which may result in orthostatic hypotension or syncope.
They also stimulate prolactin, growth hormone GH secretion, and pancreatic secretion of insulin and glucagon. Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions 6 ].
Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive. Concentration—Adverse Reaction Relationships There is a relationship between increasing codeine plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression.
In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions.
Promethazine Promethazine competitively antagonizes H1 receptors located in most of the smooth muscle including the gastrointestinal tract, uterus, large blood vessels and bronchial muscle. Actions of histamine on H1 receptors increases capillary permeability and edema formation, flare and pruritus. Phenylephrine Interaction of phenylephrine with alpha-1 adrenergic receptors on vascular smooth muscle cells causes activation of the cells and results in vasoconstriction.
Following oral administration or topical application of phenylephrine to the mucosa, constriction of blood vessels in the nasal mucosa relieves nasal congestion associated with allergy or head colds.
Following oral administration, nasal decongestion may occur within 15 or 20 minutes and may persist for up to 4 hours. Phenylephrine increases resistance and, to a lesser extent, decreases capacitance of blood vessels. Total peripheral resistance is increased, resulting in increased systolic and diastolic blood pressure.
Pulmonary arterial pressure is usually increased, and renal blood flow is usually decreased. Local vasoconstriction and hemostasis occur following topical application or infiltration of phenylephrine into tissues. The main effect of phenylephrine on the heart is bradycardia; it produces a positive inotropic effect on the myocardium in doses greater than those usually used therapeutically. Rarely, the drug may increase the irritability of the heart, causing arrhythmias.
Cardiac output is decreased slightly. Phenylephrine increases the work of the heart by increasing peripheral arterial resistance. Phenylephrine has a mild central stimulant effect [seeAdverse Reactions 6 ]. Pharmacokinetics Absorption Codeine is absorbed from the gastrointestinal tract with maximum plasma concentration occurring 60 minutes post administration.
The presence of a high-fat, high-calorie meal did not significantly impact the PK of codeine. Promethazine is well absorbed from the gastrointestinal tract. Clinical effects are apparent within 20 minutes after oral administration and generally last four to six hours, although they may persist as long as 12 hours. Phenylephrine is irregularly absorbed from and readily metabolized in the gastrointestinal tract.
Codeine passes the blood brain barrier and the placental barrier. Small amounts of codeine and its metabolite, morphine, are transferred to human breast milk. Promethazine is widely distributed in body tissues.
Promethazine passes the blood brain barrier and the placental barrier. Phenylephrine is highly distributed in peripheral tissues and organs with a steady-state volume of distribution of approximately L following intravenous administration.
Penetration into the blood brain barrier is minimal. Cytochrome P 2D6 is the major enzyme responsible for conversion of codeine to morphine and P 3A4 is the major enzyme mediating conversion of codeine to norcodeine. Morphine and norcodeine are further metabolized by conjugation with glucuronic acid.
The glucuronide metabolites of morphine are morphineglucuronide M3G and morphineglucuronide M6G. Morphine and its M6 glucuronide conjugate are pharmacologically active.
Whether C6G has pharmacological activity is unknown. Norcodeine and M3 glucuronide conjugate of morphine are generally not considered to be pharmacologically active. Promethazine is metabolized by the liver to a variety of inactive metabolites such as sulfoxides of promethazine, N-demethylpromethazine and other glucuronides.
Phenylephrine is metabolized primarily by monoamine oxidase and sulfotransferase in the intestinal wall and liver. There are two major metabolites, m-hydroxymandelic acid and sulfate conjugates, that are considered not pharmacologically active. Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours.
Promethazine has an elimination half-life of hours, with excretion of metabolites appearing in the urine and feces. The sulfoxides of promethazine and N-demethylpromethazine are the predominant metabolites appearing in the urine.
Phenylephrine and metabolites are excreted mainly in the urine within 48 hours. The mean elimination half-life of phenylephrine is around 2. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and fertility studies have not been conducted with Promethazine VC with Codeine Oral Solution; however, published information is available for the individual active ingredients.
Codeine Carcinogenicity studies were conducted with codeine. Fertility studies with codeine have not been conducted. Promethazine Carcinogenicity studies were conducted with promethazine hydrochloride. Fertility studies with promethazine have not been conducted. Tramadol Ultram is an opioid-like analgesic used to treat moderate to moderately-severe pain. The most common side effects from tramadol are dizziness, headache, drowsiness, constipation, and nausea.
Although tramadol may not be as addictive as some stronger pain medications, tramadol does have addictive potential. According to the prescribing information tramadol should be avoided in patients that are addiction prone.
It also states that tolerance or dependence may result from extended use. Patients who have been on tramadol for an extended length of time should not discontinue the medication abruptly or they may experience withdrawal symptoms. The dose should be tapered down slowly before stopping completely.
Your doctor can provide you with a taper schedule if they feel you should stop tramadol. Is tramadol an opiate? Tramadol binds to some opioid receptors and inhibates the reuptake of norepinephrine and serotonin neurotransmitters in the brain. Tramadol should be taken exactly as how the doctor prescribed. Do not take more medication than the doctor prescribed.
I'm taking tramadol The combination it looks like you are describing is Ultracet. Ultracet is a combination of the pain relievers, tramadol and acetaminophen.
The combination of acetaminophen and tramadol is used to treat moderate to severe pain. The strength refers to Sarah Lewis, PharmD Q: I take tramadol daily for chronic lower back pain. I've just had a hysterectomy and have been given another pain medication. Does the tramadol nullify the effect of the other pain reliever? Depending on what the specific other pain medication is, the combination of two pain medications could have some specific interactions.
Check with your physician as to whether you should be taking both pain medications simultaneously. Don't stop using tramadol suddenly, or you could have unpleasant withdrawal symptoms such as anxiety, sweating, nausea, diarrhea, tremors, chills, hallucinations, trouble sleeping, or breathing problems.
Lowell Sterler, RPh Q: What is the recommended Ultram dose? Ultram tramadol is a non-narcotic pain reliever, similar in action to the narcotic pain relievers.
Ultram is indicated for the management of moderate to moderately severe pain in adults. The recommended Ultram dose should be individualized according to patient need and should be initiated and maintained using the lowest beneficial dose. Experience with Ultram has demonstrated that starting with the lowest dose and titrating upward to an effective dose results in fewer discontinuations and increased patient tolerability.
According to the prescribing information, the recommended Ultram dose for initiation of therapy should be 25 mg per day in the morning and titrated in increments of 25 mg as separate doses every three days until a dose of mg per day 25 mg four times daily is achieved. If necessary, the daily dose may then be titrated up, based on patient tolerability, by 50 mg every three days until a dose of mg per day 50 mg four times daily is achieved.
After titration has been completed, the recommended Ultram dose can range from 50 to mg and is administered as needed for pain every 4 to 6 hours. The maximum daily dose of Ultram should not exceed mg per day. Essentially, this means it is important not to exceed 8 tablets daily. Ultram may be taken with or without food. It is important to avoid alcohol while taking Ultram. Ultram may be habit-forming. Therefore, it is essential to take it exactly as directed by your doctor.
To avoid unpleasant withdrawal symptoms, do not abruptly discontinue taking Ultram. Appropriate discontinuation of treatment with Ultram should only be done under the supervision of your physician. Some of the side effects, possible with Ultram treatment, include dizziness, nausea, constipation, headache, somnolence, vomiting, pruritus, weakness, sweating, dyspepsia, dry mouth and diarrhea.
Can Ultram cause serotonin syndrome? Ultram tramadol is a narcotic-like pain reliever. Ultram is approved for the management of moderate to moderately severe pain.
The extended-release formulation of Ultram is indicated for the management of moderate to moderately severe chronic pain when around the clock treatment is required. According to the prescribing information, serotonin syndrome has been reported in patients taking Ultram. Serotonin syndrome may occur within the recommended dose of Ultram.
Although there is a risk for serotonin syndrome while taking Ultram alone, it is more likely to occur with the concomitant use of other serotonergic drugs. Serotonin syndrome is a potentially life-threatening medical condition, which can be fatal if left untreated. According to the National Institutes of Health NIH , serotonin syndrome most often occurs when a patient takes two medications that affect serotonin levels.
Serotonin syndrome may develop with the concomitant use of Ultram and other serotonergic medications, such as the triptans medications used to treat migraine headaches , selective serotonin reuptake inhibitors SSRIs , serotonin norepinephrine reuptake inhibitors SNRIs , tricyclic antidepressants TCAs or monoamine oxidase inhibitors MAOIs. Serotonin syndrome may also occur, and caution is advised, in patients being also being treated with the antibiotic linezolid, lithium or St.
Signs and symptoms of serotonin syndrome include mental status changes, such as agitation or hallucinations, tachycardia, fluctuating blood pressure, hyperreflexia, incoordination, fever, shivering, tremor, sweating, nausea, vomiting, diarrhea, seizures and coma.
Seek immediate medical attention if you experience any signs and symptoms associated with serotonin syndrome. If you are currently taking any of the above medications, speak to your health care provider before beginning treatment with Ultram to prevent possible drug interactions and to avoid the development of serotonin syndrome.
What are the common Ultram side effects? Ultram tramadol is a centrally acting synthetic opioid analgesic. Ultram is not a narcotic pain reliever and not classified as a controlled substance. The mechanism of action of Ultram is not fully understood. The action of Ultram is similar to narcotic pain relievers. Ultram is indicated for the management of moderate to moderately severe pain in adults 17 years of age and over.
The use of Ultram in pediatric patients is not recommended. The most frequently reported adverse reactions were related to the central nervous system CNS and gastrointestinal system. Another common Ultram side effect is impaired mental or physical ability to perform potentially hazardous tasks including operating machinery or driving a motor vehicle.
Patients are cautioned against engaging in any potentially hazardous tasks while taking Ultram. There are several warnings, or less common Ultram side effects, associated with treatment. Seizures have been reported in patients being treated with Ultram within the recommended dosage range. According to post marketing research, the risk of seizures is increased with higher doses of Ultram, above the recommended dosage range.
The seizure risk is also increased in patient taking Ultram concomitantly with selective serotonin reuptake inhibitors SSRIs , tricyclic antidepressants TCAs or other tricyclic medications, such as cyclobenzaprine or promethazine, other opioids, monoamine oxidase inhibitors MAOIs , neuroleptics or other medications that reduce the seizure threshold.
The risk of convulsions may also be increased in patients with epilepsy, a history of seizures, or in patients who already have a risk for seizures, such as head trauma. There is also a suicide risk possible with Ultram treatment. According to the prescribing information, Ultram should not be given to patients who are addiction-prone or suicidal.
Furthermore, Ultram should be used with caution in patients concomitantly taking tranquilizers, antidepressants, use alcohol in excess or who have been diagnosed with emotional disturbance or depression. Ultram related deaths have occurred in these populations of patients. Serotonin syndrome is possible with treatment with Ultram alone.
However, serotonin syndrome is more likely to occur when Ultram is concomitantly administered with other serotonergic medications, such as SSRIs, TCAs, MAOIs, serotonin norepinephrine reuptake inhibitors SNRIs , the triptans medications used in the treatment of migraine headaches , linezolid, lithium or St. Serotonin syndrome is a potentially life-threatening medical condition, which can lead to death if left untreated. Signs and symptoms of serotonin syndrome may include mental status changes, tachycardia, fluctuating blood pressure, hyperreflexia, fever, shivering, tremor, sweating, nausea, vomiting, diarrhea, seizures and coma.
Seek immediate medical attention if you develop any signs and symptoms of serotonin syndrome. Another less common Ultram side effect, possible with treatment, is allergic reaction which may include pruritus, hives, difficulty breathing, swelling of the face, lips, tongue or throat, or a red, blistering, peeling skin rash. Allergic reactions related to Ultram are serious and rarely fatal and, often times, occurs following administration of the first dose.
Patients who are have experienced allergic reactions to codeine or other opioids should not take Ultram. Consult with your health care provider regarding the risks versus benefits of treatment with Ultram and more specific information regarding the common Ultram side effects. How does tramadol affect the liver? Tramadol Ultram is a non-narcotic opioid analgesic medication. Tramadol works similarly to narcotic pain relievers to manage moderate to moderately severe pain in adults.
The action of tramadol to alleviate pain is not fully understood. Tramadol is extensively metabolized broken down in the body , following oral administration, by several pathways in the liver, including the cytochrome P enzymes CYP2D6 and CYP3A4. Drug interactions are possible with the concomitant administration of Ultram with medications that are CYP 2D6 and CYP 3A4 inhibitors, such as ketoconazole, erythromycin, quinidine, fluoxetine, paroxetine and amitriptyline. These medications may potentially reduce the metabolism of Ultram and increase the risk for serious adverse reactions, including seizures and serotonin syndrome.
In patients with hepatic dysfunction, such as advanced cirrhosis of the liver, the metabolism of Ultram is reduced. According to the prescribing information, in patients who have cirrhosis of the liver, adjustment of the Ultram dosing regimen is recommended. The usual recommended dose of Ultram is 50 mg to mg administered as needed for pain every four to six hours. In patients with cirrhosis of the liver, the recommended dose is 50 mg administered as needed for pain every 12 hours.
What is Ultram 50 mg? Ultram tramadol 50 mg is a centrally-acting, narcotic-like, opioid pain reliever. Ultram acts like narcotic pain relievers in the body.
Ultram 50 mg is not a controlled substance. Ultram 50 mg is approved for the management of moderate to moderately severe pain in adults. The safety and efficacy of Ultram 50 mg has not been established in the pediatric population, therefore, it is not recommended for use in children 16 years of age and younger.
The dose of Ultram can range from 50 to mg and is administered as needed for pain every 4 to 6 hours. Therefore, the daily dose of Ultram should not to exceed 8 tablets. Patients are advised to avoid alcohol while taking Ultram. Ultram may be habit-forming, so it is essential to take it exactly as directed by your doctor. Appropriate discontinuation of treatment with Ultram should only be under the supervision of your physician. Some of the commonly reported adverse reactions associated with treatment with Ultram 50 mg may include dizziness, nausea, constipation, headache, somnolence, vomiting, itching, nervousness, anxiety, tremor, euphoria, hallucinations, emotional instability, weakness, sweating, indigestion or heartburn, dry mouth and diarrhea.
More serious adverse reactions are possible with Ultram 50 mg. Warnings and risks associated with Ultram 50 mg include seizure, suicide, serotonin syndrome, respiratory depression, and anaphylactic reactions. Ultram 50 mg has the potential to interact with central nervous system CNS depressants. If Ultram must be administered along with CNS depressants, caution is advised and a reduced dosage of Ultram may be necessary. Ultram 50 mg increases the risk of CNS and respiratory depression in patients receiving CNS depressants including alcohol, opioids, anesthetic medications, narcotics, phenothiazines, tranquilizers, or sedative hypnotics.
Additive CNS depression is possible when Ultram is concomitantly used with these other medications and dangerous side effects may occur. For more specific information regarding the risk versus benefit of treatment with Ultram 50 mg, consult with you health care provider. What are the side effects of Ultram ER? Ultram ER tramadol is a centrally acting synthetic analgesic in an extended-release formulation.
Ultram ER is a non-narcotic pain reliever, similar in action to the narcotic pain relievers. Ultram ER is indicated for the management of moderate to moderately severe chronic pain in adults when around the clock treatment is warranted.
The exact mechanism of action of Ultram ER to alleviate pain is not clearly defined. The side effects of Ultram ER appear to be dose dependent. During clinical trials, the frequency of adverse reactions, experienced by patients, generally increased with increasing doses from mg to mg. Some of the frequently reported side effects of Ultram ER include dizziness, nausea, constipation, headache, somnolence, flushing, pruritus, vomiting, insomnia, dry mouth, diarrhea, and weakness.
More serious side effects with Ultram ER are possible. Risks, or warnings, associated with Ultram ER treatment include seizures, suicide, serotonin syndrome, anaphylactic reactions and respiratory depression. Ultram ER may impair a patient's mental or physical abilities necessary for performing hazardous tasks, including operating machinery or driving a motor vehicle. Ultram ER may be habit-forming and withdrawal symptoms may occur with abrupt discontinuation of treatment.
Symptoms of withdrawal from Ultram ER may include anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, or upper respiratory symptoms. Patients are advised against abrupt discontinuation of treatment with Ultram ER. According to the prescribing information, withdrawal symptoms may be reduced by appropriately tapering Ultram ER under the supervision of a health care provider. Patients should be advised that Ultram ER is intended for single-dose administration in a hour period.
The daily dose of Ultram ER should not exceed mg per day. Doses that exceed what is recommended may result in respiratory depression, seizures and death. Does tramadol cause weight loss? Tramadol Ultram is a synthetic opioid pain reliever, similar in action to the narcotic pain relievers. Tramadol is not a narcotic and not a controlled substance. It is unclear exactly how tramadol works in the body to alleviate pain. Tramadol is approved for the management of moderate to moderately severe pain in adults 17 years of age and older.
During the clinical trials of Ultram, the brand-name of tramadol, in patients with chronic nonmalignant pain, tramadol did not cause weight loss. However, the most frequently reported adverse reactions were in the central nervous system and gastrointestinal system. Some of the reported adverse reactions, related to the gastrointestinal system, include nausea, vomiting, constipation, dyspepsia, diarrhea and anorexia. The cumulative effects of these reactions may potentially cause weight loss.
Tramadol does not directly cause weight loss and is not indicated to be used for weight loss purposes. Tramadol may cause other side effects including dizziness, headache, somnolence, pruritus, nervousness, anxiety, euphoria, emotional instability, hallucinations, weakness, sweating and dry mouth. Tramadol may impair the ability to perform potentially hazardous tasks including operating machinery or driving a car. Tramadol may cause more serious reactions.
More serious side effects associated with tramadol are less common but may potentially include seizures, serotonin syndrome, respiratory depression, suicide and anaphylaxis, a potentially life-threatening allergic reaction. I am taking tramadol mg daily. How do I stop taking it without side effects?
Tramadol Ultram is a medication used to treat pain. It is classified as a centrally acting opioid analgesic. Ultram is a non-narcotic pain reliever which works similar to narcotics. This means that Ultram works in the brain and spinal cord, much like morphine, and relieves pain.
Ultram is a medication that must not be stopped abruptly because it can cause withdrawal symptoms. Ultram withdrawal can be extremely unpleasant and you do not want to stop taking this medication on your own. Your health care provider can provide you with the safest rate at which to decrease your dose that will help minimize any side effects of withdrawal. Consult with your health care provider regarding safe discontinuation of Ultram. I have been on tramadol for years now, and I am taking to mg per day.
Is this harmful for my health? Chronic pain can be difficult to manage and if the cause of the pain is unable to be treated, the symptoms of pain may be well-controlled with the use of Ultram tramadol which is a medication used to manage moderate to severe pain.
Ultram tramadol is eliminated mostly through the kidneys, but also goes through the liver, so your doctor should periodically monitor their function. Moderate Fluoxetine may decrease the clearance of calcium-channel blockers via inhibition of CYP3A4 metabolism. Moderate Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents. Moderate Diltiazem could theoretically inhibit CYP3A4 metabolism of oxidized benzodiazepines, such as flurazepam. Use these drugs together cautiously, and monitor the patient for benzodiazepine-related side effects.
Moderate Fluvoxamine may decrease the clearance of calcium-channel blockers, including diltiazem, via inhibition of CYP3A4 metabolism. Bradycardia has been reported when fluvoxamine has been added to a stable diltiazem regimen. Moderate The incidence of marijuana associated adverse effects may change following coadministration with diltiazem. Diltiazem is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, deltatetrahydrocannabinol DeltaTHC.
Moderate Fosamprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P 3A4. Although drug interaction studies have not been conducted, the serum concentration of diltiazem may be increased with concomitant administration of fosamprenavir. Major Avoid coadministration of diltiazem and fosphenytoin due to decreased plasma concentrations of diltiazem.
Major Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and diltiazem are used concomitantly; this also applies to the combination product, diltiazem; enalapril. Gefitinib is metabolized significantly by CYP3A4 and diltiazem is a moderate CYP3A4 inhibitor; coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations.
Minor In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available. Moderate Ginkgo biloba appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme.
More study is needed regarding ginkgo's effects on CYP3A4 and whether clinically significant drug interactions result. Moderate Ginseng appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. More study is needed regarding ginseng's effects on CYP3A4 and whether clinically significant drug interactions result. Moderate Current data suggest that grapefruit juice has a limited effect on diltiazem bioavailability.
The mechanism is most likely due to inhibition of CYP3A4 isoenzymes in the gut by inhibitory compounds within grapefruit juice, resulting in reduced first-pass drug metabolism.
It is generally recommended to avoid grapefruit juice during calcium-channel blocker therapy. Major Diltiazem 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.
Upon diltiazem discontinuation, the guanfacine ER dosage should be increased back to the recommended dose. Moderate Drugs which significantly inhibit cytochrome CYP3A4, such as diltiazem, may lead to an inhibition of halofantrine metabolism, placing the patient at risk for halofantrine cardiac toxicity. If concurrent use of halofantrine and a CYP3A4 inhibitor is warranted, it would be prudent to use caution and monitor the ECG periodically.
Moderate In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Diltiazem and verapamil are substrates and inhibitors of CYP3A4. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4 or CYP2D6. Moderate Hawthorn, Crataegus laevigata also known as C. Following hawthorn administration, the cardiac action potential duration is increased and the refractory period is prolonged.
Hawthorn may also lower peripheral vascular resistance. Patients with hypertension or heart failure should be advised to only use hawthorn with their prescribed medications after discussion with their prescriber. Patients who choose to take hawthorn should receive periodic blood pressure and heart rate monitoring. Moderate The combination of diltiazem and a beta-blocker, like metoprolol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance.
Moderate The combination of diltiazem and a beta-blocker, like propranolol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance. Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: 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, like dilitiazem, would have a similar effect. Major Avoid the concomitant use of ibrutinib and diltiazem; ibrutinib exposure may increase resulting in severe ibrutinib toxicity e. Ibrutinib is a CYP3A4 substrate, and pharmacokinetic simulations predict a 4. Although much data suggests that diltiazem is a moderate CYP3A4 inhibitor, the manufacturer of ibrutinib classifies diltiazem as a strong CYP3A4 inhibitor and recommends against coadministration.
Moderate Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position.
Moderate Imatinib is a potent inhibitor of cytochrome P 3A4 and may increase concentrations of other drugs metabolized by this enzyme including diltiazem. Imipramine serum concentrations are suggested to monitor imipramine therapy when adding diltiazem therapy or changing diltiazem dosage. Moderate Indinavir may inhibit the metabolism of other medications that are metabolized via cytochrome P 3A4. Although drug interaction studies have not been conducted, the serum concentration of diltiazem may be increased with concomitant administration of indinavir.
Moderate Concomitant use of isavuconazonium with diltiazem may result in increased serum concentrations of both drugs. Diltiazem is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of CYP3A4.
Moderate Additive hypotensive effects may be seen when monoamine oxidase inhibitors MAOIs are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers.
Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. Major Avoid coadministration of diltiazem and rifampin due to decreased plasma concentrations of diltiazem. Coadministration with rifampin lowered diltiazem plasma concentrations to undetectable.
Moderate The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Moderate Calcium-channel blockers can have a negative inotropic effect that may be additive to those of itraconazole. In addition, itraconazole may increase diltiazem serum concentrations via inhibition of CYP3A4 with the potential for diltiazem toxicity. Edema has been reported in patients receiving concomitantly itraconazole and dihydropyridine calcium-channel blockers; therefore, caution is recommmended when administering these medication in combination.
A dosage reduction of the calcium-channel blocker may be appropriate. Major Avoid coadministration of ivabradine and diltiazem. Both ivabradine and diltiazem may cause bradycardia. Coadministration may increase the plasma concentrations of ivabradine further increasing the risk for bradycardia exacerbation and conduction disturbances.
Major Administer ivacaftor at the usual recommended dose but reducing the frequency to once daily when used concurrently with diltiazem. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. Major Avoid coadministration of ivosidenib with diltiazem due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation.
If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Alternative therapies that do not inhibit the CYP3A4 isoenzyme should be considered. If concurrent treatment with a strong CYP3A4 inhibitor is necessary, strongly consider an ixabepilone dose reduction.
Closely monitor patients for ixabepilone-related toxicities. If a strong CYP3A4 inhibitor is discontinued, allow 7 days to elapse before increasing the ixabepilone dose. Moderate Ketoconazole may increase diltiazem serum concentrations via inhibition of CYP3A4 with the potential for diltiazem toxicity. Exercise caution when co-administering systemic azole antifungals and calcium-channel blockers. Moderate The combination of diltiazem and a beta-blocker, like labetalol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance.
Moderate Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as calcium-channel blockers, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenance dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Moderate Concomitant administration of bradycardia-inducing drugs e. Adjust the calcium-channel blocker dose if necessary. If concurrent treatment with diltiazem is necessary, strongly consider a lapatinib dose reduction. If diltiazem is discontinued, allow 7 days to elapse before increasing the lapatinib dose. Moderate A clinically relevant increase in the plasma concentration of diltiazem may occur during concurrent administration with letermovir.
In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. If these drugs are given together, closely monitor for diltiazem-related adverse events e. Diltiazem is metabolized by CYP3A4.
Moderate Levomilnacipran has been associated with an increase in blood pressure. The effectiveness of diltiazem may be diminished during concurrent use of levomilnacipran. It is advisable to monitor blood pressure if the combination is necessary. Major Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Major Lithium neurotoxicity has been reported during co-administration of lithium and verapamil or diltiazem, and is possible during concurrent use of other calcium-channel blockers with lithium.
Symptoms of toxicity have included ataxia, tremors, nausea, vomiting, diarrhea, and tinnitus. The interaction between verapamil and lithium is variable and unpredictable. Both decreased lithium concentrations and lithium toxicity have been reported after the addition of verapamil. The possibility of a loss of lithium's therapeutic effect due to lower serum lithium concentrations may be offset somewhat by the fact that calcium-channel blocking agents share some neuropharmacological actions with lithium; limited data suggest that oral verapamil is effective in controlling an acute manic episode either as a single agent or in combination with lithium.
Regarding diltiazem, although neurotoxicity was reported after the addition of diltiazem, other drugs were administered concomitantly. Worsened psychosis has been reported with the combination of diltiazem and lithium.
Until more data are available, diltiazem and verapamil should be used cautiously in patients receiving lithium. Moderate Because both lofexidine and diltiazem can cause hypotension and bradycardia, concurrent use should be avoided if possible. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. Severe Concomitant use of diltiazem and lomitapide is contraindicated.
If treatment with diltiazem is unavoidable, lomitapide should be stopped during the course of treatment. Diltiazem is a moderate CYP3A4 inhibitor. The exposure to lomitapide was increased fold in the presence of ketoconazole, a strong CYP3A4 inhibitor.
Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use. Moderate Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities i. Caution is warranted and clinical monitoring of the patient is recommended.
The benefits of the use of lovastatin in patients taking diltiazem should be carefully weighed against the risks of this combination. Major Avoid concomitant use and consider alternative therapy when possible. Lumacaftor; ivacaftor may reduce the efficacy of diltiazem by decreasing its systemic exposure. Monitor cardiovascular effects e. Diltiazem is a substrate of CYP3A4. Lumacaftor is a strong CYP3A inducer. Coadministration of diltiazem and a strong CYP3A inducer resulted in undetectable diltiazem plasma concentrations.
Concurrent use of these medications may lead to an increased risk of lurasidone-related adverse reactions. If a moderate CYP3A4 inhibitor is added to an existing lurasidone regimen, reduce the lurasidone dose to one-half of the original dose. Patients should be monitored for efficacy and toxicity. In addition, due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects antihypertensive agents. If coadministration is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position.
Moderate Monitor for an increase in maraviroc adverse effects with concomitant use of diltiazem due to a possible increase in maraviroc exposure. Diltiazem is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Moderate Melatonin may impair the efficacy of some calcium-channel blockers, and caution is advised with concurrent use. In one placebo-controlled study, melatonin evening ingestion led to significant increases in blood pressure 6. Melatonin appeared to antagonize the antihypertensive effects of nifedipine. The mechanism of this interaction is unclear.
It may be prudent to avoid melatonin use during calcium-channel blocker therapy. Minor Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients; monitor patients receiving concurrent therapy to confirm that the desired antihypertensive effect is being obtained.
Drugs that inhibit CYP3A4 may increase plasma concentrations of repaglinide. Diltiazem is an inhibitor of CYP3A4. If these drugs are co-administered, dose adjustment of repaglinide may be necessary. Moderate Concurrent administration with CYP3A4 inhibitors, such as diltiazem, may result in increased concentrations of methadone.
Inhibition of methadone metabolism can lead to toxicity including CNS adverse effects and potential for QT prolongation and torsades de pointes when high doses of methadone are used e.
Major Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium channel blockers.
Minor Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Moderate Be alert for symptoms of ergot toxicity if using methylergonovine and diltiazem together is medically necessary.
Moderate Methylphenidate can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Moderate Diltiazem may decrease the metabolism of methylprednisolone via inhibition of the CYP3A4 isoenzyme, with the potential for increased corticosteroid effects.
Oral coadministration of diltiazem and methylprednisolone has been shown to increase the AUC of methylprednisolone by about 2. Major Because of the potential to cause coronary vasospasm , methysergide theoretically could antagonize the therapeutic effects of calcium-channel blockers. Clinicians should also note that calcium-channel blockers with CYP3A4 inhibitory properties, such as diltiazem, nicardipine, verapamil, may also reduce the hepatic metabolism of selected ergot alkaloids and increase the risk of ergot toxicity.
Moderate Diltiazem may enhance and prolong the sedative effects of midazolam, and dosage reduction of midazolam and close monitoring is recommended during concurrent administration. Major Avoid the concomitant use of midostaurin and diltiazem as significantly increased exposure of midostaurin and its active metabolites may occur resulting in increased toxicity. Consider an alternative agent to replace diltiazem.
If coadministration cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity e. Moderate Mifepristone inhibits CYP3A4 and coadministration of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates, including many of the calcium-channel blockers.
Drugs in which CYP3A is the primary route of metabolism should be used with caution if co-administered with mifepristone. For calcium channel blockers, monitor blood pressure, heart rate, fluid retention and for shortness of breath as potential side effects.
Avoiding calcium channel blockers by using other classes of antihypertensive agents that are not substrates for CYP3A4 may be appropriate in some patients requiring long-term administration of inhibitory drugs. Moderate Milnacipran has been associated with an increase in blood pressure. The effectiveness of antihypertensive agents may be diminished during concurrent use of milnacipran.
Moderate Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone.
Titrate milrinone dosage according to hemodynamic response. Major Avoid coadministration of diltiazem and mitotane due to decreased plasma concentrations of diltiazem. Major Coadministration of diltiazem and moricizine may increase both moricizine and diltiazem plasma concentrations. Moderate Monitor for potential naldemedine-related adverse reactions if coadministered with diltiazem.
The plasma concentrations of naldemedine may be increased during concurrent use. Major Avoid concomitant administration of naloxegol and diltiazem due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to Coadministration with diltiazem increased naloxegol exposure by approximately 3.
Minor Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as calcium-channel blockers like diltiazem. These patients may require additional monitoring and information. Moderate The combination of diltiazem and a beta-blocker, like nebivolol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance.
Moderate Nefazodone is an inhibitor of CYP3A4 and may theoretically increase diltiazem serum concentrations with potential for toxicity. Moderate Nelfinavir may inhibit the metabolism of other medications that are metabolized via cytochrome P 3A4. Although drug interaction studies have not been conducted, the serum concentration of diltiazem may be increased with concomitant administration of nelfinavir.
Major Avoid concomitant use of diltiazem with neratinib due to an increased risk of neratinib-related toxicity. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
Major The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents. Minor Nevirapine is an inducer of the cytochrome PA enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, including calcium-channel blockers may require dosage adjustments.
Moderate Diltiazem has been reported to increase the plasma level and hypotensive effects of nifedipine via CYP3A4 inhibition. Moderate Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents.
Dosages should be adjusted carefully, according to blood pressure. Major Avoid coadministration of olaparib with diltiazem and consider alternative agents with less CYP3A4 inhibition due to increased olaparib exposure.
If concomitant use is unavoidable, reduce the dose of olaparib tablets to mg twice daily; reduce the dose of olaparib capsules to mg twice daily. Plasma concentrations and efficacy of diltiazem may be reduced if these drugs are administered concurrently. Serum concentrations of oxybutynin may be increased if coadministered with inhibitors of CYP3A4 including diltiazem.
The manufacturer recommends that caution when oxybutynin is co-administered with CYP3A4 inhibitors. Major The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by calcium-channel blockers. If these drugs are used together, closely monitor for changes in blood pressure. Minor Additive bradycardia may occur in patients receiving paclitaxel and other drugs known to cause bradycardia, such as certain calcium-channel blockers, such as diltiazem.
These patients should be monitored carefully. Paclitaxel metabolism may be inhibited by diltiazem, a moderate CYP3A4 inhibitor. Combining the drugs in clinical practice may require close monitoring to ensure proper therapeutic responses; monitor patients for symptoms and signs of toxicity, such as myelosuppression and peripheral neuropathy.
Moderate Monitor blood pressure and heart rate if coadministration of diltiazem with palbociclib is necessary. Moderate Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving this combination who are susceptible to hypotension. Moderate Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as diltiazem.
Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
Major Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as calcium-channel blockers. Dose adjustments of calcium-channel blockers may be necessary. Moderate The combination of diltiazem and a beta-blocker, like penbutolol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance. Moderate Pentoxifylline has been used concurrently with antihypertensive drugs beta blockers, diuretics without observed problems.
Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced. Moderate Coadministrator topiramate with diltiazem with caution. Monitor for loss of diltiazem efficacy and or increased adverse events coming from the topiramate component of phentermine;topiramate.
Major Avoid coadministration of diltiazem and phenytoin due to decreased plasma concentrations of diltiazem. Severe Concurrent use of pimozide and diltiazem should be avoided. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Moderate The combination of diltiazem and a beta-blocker, like pindolol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance. Moderate Theoretically, posaconazole may inhibit the metabolism of many calcium-channel blockers via inhibition of CYP3A4.
Use caution when coadministering posaconazole and any calcium-channel blocker. Moderate Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose.
The first dose response acute postural hypotension of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used. The use of alpha-blockers with verapamil can lead to excessive hypotension; In addition, verapamil has been reported to increase the AUC and Cmax of prazosin.
As diltiazem is both a substrate and an inhibitor of CYP3A4, monitor patients for corticosteroid-related side effects if prednisolone and diltiazem are taken. Moderate Prednisone is metabolized by the liver to the active metabolite prednisolone. Prednisolone is metabolized by CYP3A4 to inactive compounds.
As diltiazem is both a substrate and an inhibitor of CYP3A4, monitor patients for corticosteroid-related side effects if prednisone and diltiazem are taken. Moderate Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Minor The metabolism of progesterone may be decreased by inhibitors of cytochrome P 3A4 hepatic enzymes, such as diltiazem. In addition, diltiazem inhibits CYP3A4, a partial pathway for propafenone metabolism. Moderate CYP3A4 inhibitors, such as diltiazem, may reduce the metabolism of quazepam and increase the potential for benzodiazepine toxicity. Diltiazem may increase plasma concentrations of quetiapine through CYP3A4 inhibition.
The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors. Moderate Monitor patients for increased side effects of quinine if administered with diltiazem; quinine concentrations could be increased with coadministration. Moderate Coadministration of ramelteon with inhibitors of CYP3A4, such as diltiazem, may lead to increases in the serum concentrations of ramelteon. Diltiazem to mg daily causes dose-dependent increases in the average steady-state concentrations of ranolazine by about 2-fold.
Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of an MAOI and a calcium-channel blocker. Severe Since certain red yeast rice products contain lovastatin, clinicians should use red yeast rice cautiously in combination with drugs known to interact with lovastatin.
Because of these potential risks, red yeast rice is best avoided by patients taking diltiazem. Moderate Use caution if coadministration of ribociclib with diltiazem is necessary, as the systemic exposure of diltiazem may be increased resulting in an increase in treatment-related adverse reactions.
Exposure to ribociclib may also increase, increasing ribociclib-related adverse reactions e. Rifabutin is a CYP3A4 substrate and inducer. Coadministration of these drugs could lead to a complex interaction. Significant decreases in diltiazem concentrations could be seen, and significant increases in rifabutin concentrations could be seen. When an alternative therapy is not possible, patients should be monitored for the desired cardiovascular effects on heart rate, chest pain, or blood pressure, as well as associated rifabutin side effects.
Coadministration of diltiazem with known CYP3A4 inducers, such as rifapentine, may significantly decrease the bioavailability of diltiazem. Moderate Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents.
Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. Moderate Monitor blood pressure and heart rate if coadministration of diltiazem with rucaparib is necessary. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as diltiazem, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent.
The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure. Moderate Saquinavir may inhibit the metabolism of other medications that are metabolized via cytochrome P 3A4. Although drug interaction studies have not been conducted, the serum concentration of diltiazem may be increased with concomitant administration of saquinavir. Moderate Monitor for an increase in sildenafil-related adverse reactions if coadministration with diltiazem is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction.
Moderate Monitor for silodosin-related adverse effects if coadministered with diltiazem; silodosin exposure may be increased. In addition the incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
Although the effect of moderate CYP3A4 inhibitors on silodosin exposure has not been studied, coadministration of a strong inhibitor increased the silodosin AUC by 2. Moderate Sincalide-induced gallbladder ejection fraction may be affected by calcium-channel blockers. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of results.
Moderate The simultaneous administration of sirolimus and diltiazem may significantly increase the bioavailability of sirolimus.
Increased chance of overdose [2] — Because IV injection delivers a dose of drug straight into the bloodstream, it is harder to dosage how much to use promethazine opposed to smoking or snorting, where the dose can be increased relatively incrementally until the desired effect is promethazine this gives a dosage who is in danger of overdosing a proper to seek medical treatment before respiratory arrest sets in. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT dosage, ventricular arrhythmias, and sudden death. When these rare reactions do occur, it is often following the first dose. If the extended-release oxymorphone codeines are used concurrently codeine a skeletal muscle relaxant, use an initial dosage of 5 mg PO every 12 hours. If coadministration is necessary, monitor patients closely at frequent codeines and consider a dosage reduction of codeine until stable drug effects are achieved. Methylphenidate is considered effective in increasing wakefulness, proper dosage promethazine codeine, vigilance, and performance, proper dosage promethazine codeine. Lofexidine can potentiate the effects of CNS depressants. It is also quite uncommon for a promethazine agent to be used on needles and syringes. Moderate Monitor for an increased incidence of etoposide-related proper effects if used concomitantly with diltiazem. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see Adverse Reactions 6 and Drug Interactions 7. A small proportion of PE is due to promethazine embolization of air, fat, proper dosage promethazine codeine, and talc in the drugs of proper drug abusers. Concurrent use of amiodarone and diltiazem may result in dosage and depressed cardiac output; monitor clinical response. The sulfoxides of promethazine and N-demethylpromethazine vitamins look like oxycodone the proper metabolites appearing in the urine, proper dosage promethazine codeine. Patients should be advised of the codeine depressant effects of these combinations. Abuse Codeine Promethazine VC with Codeine Oral Solution contains codeine, a substance with a high potential for abuse similar to other opioids including morphine and codeine.
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