Phentermine dosage forms for naproxen sodium

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phentermine dosage forms for naproxen sodium

Persons taking an anticonvulsant should discuss the use of herbal supplements with their health care professional prior to consuming them. Send the page " " to a friend, relative, colleague or yourself. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Use caution when topiramate is prescribed with agents known to predispose patients to similar heat-related disorders such as trospium. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. The resulting solution can be encapsulated in a softgel capsule using the appropriate gel mass. Journal of Clinical Psychopharmacology 24 4:

: Phentermine dosage forms for naproxen sodium

Buy phentermine 37.5 online canadian pharcharmy online hydrocodone Additonally, phentermine sodium a weak ability to dose-dependently raise serotonin levels. Conditions that sodium predispose patients to acidosis [i. Monitor renal status, especially in patients with conditions naproxen renal prostaglandins have a supportive role in the maintenance of renal dosage. Major Phentermine safety and efficacy of coadministration of lorcaserin dosage other products intended for weight loss including prescription drugs e. In some embodiments the at least for phenternine layer has a substantially higher dissolution rate than at least one of phentermine pharmaceutical layers. Forms study is needed to forms the magnitude and cliniical significance of any pharmacokinetic or pharmacodynamic interactions. Some pharmaceutical applications separate potentially interacting naproxen from one for within a tablet.
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Similar precautions apply to combination products containing topiramate such as phentermine; topiramate. Moderate The combination of bromocriptine with phentermine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phentermine should be approached with caution. Moderate Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.

Moderate Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics e. Monitor baseline and periodic potassium concentrations during coadministration. Moderate Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect.

Major Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, such as phentermine, may be associated with an increased seizure risk; therefore, seizures may be more likely to occur in patients receiving this weight loss aide with bupropion. Patients should be closely monitored if this combination is necessary. Do not combine therapy with phentermine or phentermine-combinations and bupropion; naltrexone due to this risk and the duplication of therapy for weight loss.

Moderate Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as carbamazepine, barbiturates, or phenytoin, as well as fosphenytoin and ethotoin. Minor In theory, an interaction is possible between cabergoline, an ergot derivative, and some sympathomimetic agents such as vasopressors e.

Use of the ergot derivative bromocriptine for lactation suppression in conjunction with a sympathomimetic i. Major Avoid concurrent use of acetazolamide or methazolamide with topiramate. Topiramate is a weak carbonic anhydrase inhibitor. Concomitant use of topiramate with acetazolamide or methazolamide may create a physiological environment that increases the risk of renal stone formation associated with topiramate use. Additionally, through an additive effect, the use of topiramate with agents that may increase the risk for heat-related disorders acetazolamide and methazolamide , may lead to oligohidrosis, hyperthermia and heat stroke.

Major Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics. Concurrent use of cariprazine with CYP3A4 inducers, such as topiramate, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear. Moderate Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding.

Moderate The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. Major Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. Choline Salicylate; Magnesium Salicylate: Moderate Concurrent use of topiramate and drugs that affect platelet function such as cilostazol may increase the risk of bleeding.

In addition, cilostazol is metabolized by the cytochrome P CYP2C19 hepatic isoenzyme and may interact with medications that are inhibitors of CYP2C19, including topiramate. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors.

In addition, concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors SSRIs may increase the risk of bleeding. Major Topiramate may reduce the antiplatelet activity of clopidogrel by inhibiting clopidogrel's metabolism to its active metabolite. Use clopidogrel and topiramate together with caution and monitor for reduced efficacy of clopidogrel. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps; the CYP2C19 isoenzyme is involved in both steps.

Topiramate is an inhibitor of CYP2C Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Moderate Caution is warranted when elvitegravir is administered with topiramate as there is a potential for decreased elvitegravir concentrations. Elvitegravir is a CYP3A4 substrate. Moderate If concurrent use of cobimetinib and topiramate is necessary, use caution and monitor for decreased efficacy of cobimetinib.

Guidance is not available regarding concomitant use of cobimetinib with weak CYP3A inducers. Minor The response to sympathomimetics may be enhanced by colchicine. Major Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate.

Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy HRT should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. Minor The metabolism of dapsone may be accelerated when administered concurrently with topiramate, a known inducer of CYP3A4.

Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine a metabolite associated with hemolysis. If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia. Moderate Caution is warranted when darunavir is administered with topiramate as there is a potential for decreased concentrations of darunavir. Darunavir is a substrate of CYP3A4. Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Moderate Concurrent administration of topiramate with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in decreased concentrations of dasabuvir, paritaprevir, and ritonavir.

Ritonavir, paritaprevir, and dasabuvir minor are all metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. Moderate Concurrent administration of topiramate with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in decreased concentrations of dasabuvir, paritaprevir, and ritonavir. Moderate Concurrent administration of topiramate with ritonavir may result in decreased concentrations of ritonavir.

Ritonavir is metabolized by this enzyme. Moderate Delavirdine is a potent inhibitor of cytochrome P 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions. Major Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery.

Moderate Use phentermine and selective serotonin reuptake inhibitors SSRIs or serotonin norepinephrine reuptake inhibitors SNRIs together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended.

Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents.

In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants e. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. Moderate Use dichlorphenamide and topiramate, another carbonic anhydrase inhibitor, together with caution as both drugs can cause metabolic acidosis.

Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. Although the clinical relevance has not been determined, the clinician should be aware that serum digoxin concentrations may be affected when digoxin and topiramate are used concomitantly. 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. Moderate Close clinical monitoring is advised when administering topiramate with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Topiramate is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme.

Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of topiramate and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy.

Moderate Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.

Moderate Use caution if coadministration of dronabinol with topiramate is necessary, and monitor for a decrease in the efficacy of dronabinol. Concomitant use may result in decreased plasma concentrations of dronabinol. Dronedarone is metabolized by CYP3A. Coadministration of CYP3A4 inducers, such as topiramate, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy.

Drospirenone; Ethinyl Estradiol; Levomefolate: Major Coadministration of dyphylline with sympathomimetics should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias, and should be avoided if possible. Moderate Caution is advised when administering elbasvir with topiramate. Use of these drugs together may decrease the plasma concentrations of elbasvir and could result in decreased virologic response.

Moderate Caution is advised when administering elbasvir; grazoprevir with topiramate. Use of these drugs together may decrease the plasma concentrations of grazoprevir and could result in decreased virologic response. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended. Emtricitabine; Rilpivirine; Tenofovir alafenamide: Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: Major Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly.

Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. Major Topiramate can increase the clearance of estrogens and compromise the efficacy of estrogens used as hormone replacement therapies or contraceptives. Patients taking oral contraceptives, non-oral combination contraceptives, or progestions for contraception or patients taking estrogens or progestins for hormone replacement therapy should report changes in their bleeding patterns to their prescribers.

Dosages of the products may need adjustment; the manufacturer of topiramate recommends that an oral contraceptive containing 50 mcg of ethinyl estradiol be used. Major Ethanol consumption is contraindicated within 6 hours prior to and 6 hours after administration of topiramate extended-release capsules. The pattern of topiramate release from the extended-release capsule is significantly altered in the presence of alcohol.

This may result in significantly increased plasma levels of topiramate soon after dosing followed by subtherapeutic levels later in the day. Because of the possibility of additive CNS depressant effects, other dosage formulations of topiramate should be used with extreme caution if used in combination with alcohol. Ethinyl Estradiol; Ethynodiol Diacetate: Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: Ethinyl Estradiol; Norethindrone Acetate: Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Moderate Monitor for clinical efficacy of etoposide if used concomitantly with topiramate.

Coadministration of etoposide with a strong CYP3A4 inducer phenytoin resulted in increased etoposide clearance and reduced efficacy, as did coadministration with a weak inducer of CYP3A4 and P-glycoprotein P-gp valproic acid. Moderate Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant ezogabine, may increase the risk of bleeding. Moderate Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant felbamate may increase the risk of bleeding.

Major The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as topiramate is not recommended. Moderate Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors SSRIs like fluoxetine may increase the risk of bleeding.

Moderate Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. Moderate Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use.

Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. Moderate Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors SSRIs like fluvoxamine may increase the risk of bleeding. Moderate Topiramate may influence the pharmacokinetic profile of cannabinoids in Marijuana and may also influence the pharmacodynamic profile. This may result in an altered adverse event profile of one or both drugs.

Topiramate is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, deltatetrahydrocannabinol THC. More study is needed to determine the magnitude and cliniical significance of any pharmacokinetic or pharmacodynamic interactions. Additive drowsiness and CNS depression is possible. Monitor for changes in moods or behaviors, or for other CNS effects.

Moderate Monitor for clinical response of gefitinib if used concomitantly with topiramate. Gefitinib is metabolized significantly by CYP3A4 and topiramate is a weak CYP3A4 inducer; coadministration may increase gefitinib metabolism and decrease gefitinib concentrations. This also applies to combination products containing topiramate, such as phentermine; topiramate.

Minor Coadministration of glyburide with topiramate may decrease systemic exposure to glyburide. A pharmacokinetic drug interaction study evaluated the combination of topiramate and glyburide. Reductions in AUC and Cmax were noted for glyburide and the active metabolites. Major Some, but not all, green tea products contain caffeine. Additive CNS stimulant effects are likely to occur when caffeine is coadministered with other CNS stimulants or psychostimulants. Caffeine should be avoided or used cautiously with phentermine.

Major Caffeine, an active constituent of guarana, is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Use of guarana should be avoided with amphetamine, dextroamphetamine, methylphenidate, modafinil, pemoline, pseudoephedrine, beta-agonists or other sympathomimetics. Topiramate may increase phenytoin concentrations through its inhibitory effects on CYP2C These patients were generally receiving dosage regimens of phenytoin twice-daily.

Major Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as methyldopa. Concomitant use of phentermine with methyldopa may antagonize the antihypertensive effects of these agents. Although leading drug interaction texts differ in the potential for an interaction between phentermine and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.

Moderate Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as topiramate. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. Moderate Imatinib is a potent inhibitors of cytochrome P 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions. Moderate Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

Caution and close observation is needed if indacaterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. Moderate Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly.

Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Major Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. Moderate Caution and close monitoring are warranted when isavuconazonium is administered with topiramate as there is a potential for decreased concentrations of isavuconazonium.

Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of this enzyme. Severe In general, all types of sympathomimetics and psychostimulants should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and even respiratory sympathomimetics e.

Some local anesthetics also contain a sympathomimetic e. In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. Major Avoid coadministration of ivabradine and topiramate. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure. Moderate Use caution when administering ivacaftor and topiramate concurrently; the clinical impact of this interaction has not yet been determined.

Administration of ivacaftor with strong CYP3A inducers is not recommended because sub-therapeutic ivacaftor exposure could result; the impact of mild inducers is not known. Kava Kava, Piper methysticum: While the interactions can be pharmacodynamic in nature, kava kava has been reported to inhibit many CYP isozymes i. Persons taking an anticonvulsant should discuss the use of herbal supplements with their health care professional prior to consuming them.

Moderate Use caution when coadministering lamotrigine and topiramate. Concurrent use of topiramate and drugs that cause thrombocytopenia, such as lamotrigine, may increase the risk of bleeding. Concurrent use may also result in significant CNS depression. Plasma concentrations of lamotrigine do not appear to be affected by the combined use of the drugs. Moderate Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant levetiracetam, may increase the risk of bleeding.

Moderate Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.

The reduction in TSH secretion is not sustained; hypothyroidism does not occur. Major Phentermine should not be administered during or within 14 days following the use of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase MAO. Drugs that possess MAO-inhibiting activity, such as linezolid, can prolong and intensify the cardiac stimulation and vasopressor effects of phentermine which may invoke a hypertensive reaction.

Additonally, phentermine has a weak ability to dose-dependently raise serotonin levels. Linezolid has the potential for interaction with serotonergic agents, which may increase the risk for serotonin syndrome. If coadministration is necessary, closely monitor for increased blood pressure and signs of serotonin syndrome. Lithium levels should be monitored; monitor patients for adequate control of symptoms when phentermine; topiramate is added to lithium therapy.

Moderate The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with topiramate. Loperamide is metabolized by the hepatic enzyme CYP3A4; topiramate is a mild inducer of this enzyme. Major The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs e. Some of these agents fenfluramine, dexfenfluramine are known to increase the risk for cardiac valvulopathy and pulmonary hypertension.

Coadministration of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome. Low Molecular Weight Heparins: Moderate Because lurasidone is primarily metabolized by CYP3A4, decreased plasma concentrations of lurasidone may theoretically occur when the drug is co-administered with inducers of CYP3A4 such as topiramate.

Major Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy if taking macitentan with a sympathomimetic. Moderate Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.

Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy. Minor Use caution if coadministration of maraviroc with topiramate is necessary, due to a possible decrease in maraviroc exposure. Monitor for a decrease in maraviroc efficacy with concomitant use. Moderate Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control.

Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine. Major Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. Methenamine; Sodium Acid Phosphate: Major Because of the potential risk and severity of serotonin syndrome, caution should be observed during co-administration of mirtazapine with other drugs that have serotonergic properties.

As a drug related to the amphetamines, phentermine has the potential to cause serotonin syndrome when combined with serotonergic agents. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes e. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. Mirtazapine should be discontinued if a patient develops a combination of symptoms suggestive of serotonin syndrome.

Moderate Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.

Moderate Concurrent use of nabilone with sympathomimetics e. In a study of 7 adult males, combinations of cocaine IV and smoked marijuana 1 g marijuana cigarette, 0 to 2. Major Avoid coadministration of nisoldipine with topiramate due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.

Major Concomitant use of nitrates with sympathomimetics can result in antagonism of the antianginal effects of nitrates. In addition, amyl nitrite can block the alpha-adrenergic effects of epinephrine, possibly precipitating tachycardia and severe hypotension. Moderate Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants.

A mechanism for the potential interaction has not been stated. Moderate The safety and efficacy of coadministration of phentermine with other products intended for weight loss has not been established. Moderate Coadministration of carbamazepine has resulted in a clinically significant decrease in topiramate exposure; a topiramate dosage increase may be necessary. Additionally, concurrent use of topiramate and drugs that cause thrombocytopenia, such as carbamazepine, may also increase the risk of bleeding; monitor patients appropriately.

Moderate Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors SSRIs like paroxetine may increase the risk of bleeding. Moderate Coadministration of pazopanib and topiramate may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly. Pazopanib is a substrate for CYP3A4. Topiramate in a weak CYP3A4 inducer. Major A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents.

Dosage adjustments of anticonvulsants may be necessary during simultaneous use of these drugs. Topiramate is an inducer of CYP3A4, while perampanel is a substrate of this enzyme. Patients taking topiramate who begin treatment with perampanel should be closely monitored for adverse effects and receive a higher initial dose of perampanel. Addition or withdrawal of enzyme-inducing antiepileptic drugs may require a perampanel dose adjustment.

Severe Phendimetrazine is a phenylalkaline sympathomimetic agent. All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The safety of phendimetrazine when used with other anorexiants such as phentermine is controversial and concurrent use should be avoided. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia.

Similarly, phendimetrazine should not be used in combination with OTC preparations and herbal products that may contain ephedra alkaloids or Ma huang. Major Concurrent use of phentermine and phenothiazines may antagonize the anorectic effects of phentermine. In addition, psychostimulants can aggravate psychotic states. Moderate Caution and close observation should also be used when pirbuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects.

Moderate Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant pregabalin, may increase the risk of bleeding. Minor Probenecid may increase the renal clearance of topiramate resulting in lower topiramate concentrations. Although not evaluated in humans, animal studies using probenecid along with topiramate showed a significant increase in renal clearance of topiramate.

This suggests that topiramate may undergo renal tubular reabsorption. Probenecid may block renal tubular reabsorption of topiramate, thus increasing the renal clearance of the drug. Major Because procarbazine exhibits some monoamine oxidase inhibitory MAOI activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects.

In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary e. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced.

Patients should be counseled to avoid non-prescription OTC decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. Moderate The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra.

Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors MAOIs , hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B MAO-B inhibition of rasagiline at manufacturer recommended doses.

One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses.

Major Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as reserpine. Concomitant use of phentermine with reserpine may antagonize the antihypertensive effects of these agents. Moderate Use caution if coadministration of ribociclib with topiramate is necessary, as the systemic exposure of ribociclib may decrease resulting in decreased efficacy. Patients should be monitored for reduced efficacy if taking riociguat with a sympathomimetic.

Moderate Concurrent use of topiramate and anticoagulants may increase the risk of bleeding. However, coadministration of rivaroxaban and topiramate may result in decreased rivaroxaban exposure and may decrease the efficacy of rivaroxaban. If these drugs are administered concurrently, monitor the patient for signs of bleeding or lack of efficacy of rivaroxaban. Coadministration of a CYP3A4 inducer, like topiramate, may decrease systemic concentrations of romidepsin. Use caution when concomitant administration of these agents is necessary.

Moderate Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant rufinamide, may increase the risk of bleeding. Moderate Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors MAOIs , such as safinamide, and sympathomimetic medications, such as phentermine. If concomitant use of safinamide and phentermine is necessary, monitor for hypertension and hypertensive crisis.

Selective serotonin reuptake inhibitors: One case report has been received of adverse reactions with phentermine and fluoxetine. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies. Patients should be monitored for reduced efficacy if taking selexipag with a sympathomimetic. Serotonin norepinephrine reuptake inhibitors: Moderate Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors SSRIs like topiramate may increase the risk of bleeding.

Severe Sibutramine is contraindicated in patients taking other centrally-acting appetite suppressant drugs, such as phentermine. In addition, many of these agents enhance central serotonergic activity by various mechanisms. Concurrent use of sibutramine with other serotonergic agents may increase the potential for serotonin syndrome or neuroleptic malignant syndrome-like reactions.

Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes e. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Major Avoid concurrent use of simeprevir and topiramate. Induction of CYP3A4 by topiramate may significantly reduce the plasma concentrations of simeprevir, resulting in treatment failure. Severe Because phentermine is a sympathomimetic and anorexic agent, it should not be used in combination with other psychostimulants.

Major Use caution when administering velpatasvir with topiramate. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. John's Wort, Hypericum perforatum: John's wort Hypericum perforatum may reduce the neuronal uptake of monoamines and should be used cautiously with sympathomimetics. Topiramate may affect the metabolism of tamoxifen to these metabolites; plasma concentrations of tamoxifen its active metabolites have been reduced when coadministered other CYP3A4 inducers.

The clinical significance of this interaction is not known. If coadministration is necessary, monitor for tamoxifen efficacy. Moderate Caution is warranted with the concurrent use of tedizolid and phentermine. Tedizolid is an antibiotic that is also a weak reversible, non-selective inhibitor of MAO which could potentially prolong and intensify the cardiac stimulation and vasopressor effects of phentermine.

Phentermine should not be administered during or within 14 days following the use of drugs with MAO-inhibiting activity. Moderate Caution is warranted when topiramate is administered with telithromycin as there is a potential for decreased telithromycin concentrations and loss of efficacy. Telithromycin is a substrate of CYP3A4. Moderate Caution is advised when administering terbinafine with topiramate.

In some embodiments a layer comprises a conical section of a pharmaceutical formulation. In some embodiments a layer comprises an elliptical section of a pharmaceutical formulation. In some embodiments a layer comprises a sideways section of a pharmaceutical formulation. In some embodiments a layer comprises a cubical section of a pharmaceutical formulation. In some embodiments a layer comprises a wedge of a pharmaceutical formulation. In some embodiments a layer comprises a substantial portion of a pharmaceutical formulation.

In some embodiments at least one pharmaceutical layer reacts when brought into contact with another of the pharmaceutical layers within the layered pharmaceutical formulation. In some embodiments at least one pharmaceutical layer does not react when brought into contact with another of the pharmaceutical layers. In some embodiments an intermediate layer is configured to dissolve in vivo. Dissolving is the act of solvation wherein a solute is dissolved in a solvent to create a solution.

Dissolving in vivo means that the dissolving takes place within an organism or within living tissue either taken from or part of an organism. An organism is any living animal, plant, bacteria or fungus. In preferred embodiments the organism is human. In some embodiments a dissolving intermediate layer separates at least two of the pharmaceutical layers. In some embodiments the two pharmaceutical layers contain different pharmaceutical compositions. In some embodiments after the intermediate layer dissolves, the pharmaceutical layers are no longer held together within the pharmaceutical formulation.

In some embodiments after the intermediate layer dissolves, the pharmaceutical layers remain substantially intact. In some embodiments each pharmaceutical layer has a different dissolution rate. A dissolution rate is the salvation of a pharmaceutical layer volume per unit time. In some embodiments one or more pharmaceutical layers have similar dissolution rates.

Preferably the one or more intermediate layers have a higher dissolution rate than the two or more pharmaceutical layers. The pharmaceutical formulation comprises two pharmaceutical layers A and B. Pharmaceutical layer A comprises a pharmaceutical composition. In some embodiments of the pharmaceutical formulation , the pharmaceutical layer B comprises the same pharmaceutical composition as that of the pharmaceutical layer A. In the illustrated embodiment of pharmaceutical formulation , the pharmaceutical layer A comprises a different pharmaceutical composition than that of the pharmaceutical layer B.

The pharmaceutical formulation also comprises an intermediate layer In the illustrated embodiment the intermediate layer is configured to dissolve in vivo. Each of the pharmaceutical layers A and B comprises one or more pharmaceutical compositions. As illustrated in the pharmaceutical formulation , the dosage amount of each pharmaceutical layer A and B is similar.

The dosage strength of each pharmaceutical layer may also be similar. This difference in dosage amount or strength allows for individualized treatment of symptoms that are addressed by increasing or decreasing a dosage of one or more pharmaceutical layers while maintaining a dosage of other layers. The amount or strength of dosage of a drug contained within a pharmaceutical formulation will, of course, be dependent on the subject being treated, on the subject's weight, the severity of the affliction, the manner of administration and the judgment of the prescribing physician.

Specifically, the illustrated pharmaceutical layer A comprises zonisamide and the pharmaceutical layer B comprises bupropion. The intermediate layer comprises lactose or a suitable monosaccharide sugar, disaccharide sugar or a starch. In another embodiment, one or more of the pharmaceutical layers comprises naltrexone, one or more of the pharmaceutical layers comprises bupropion, and at least one intermediate layer comprises a monosaccharide sugar, a disaccharide sugar or a starch.

In another embodiment, one or more of the pharmaceutical layers comprises naltrexone, one or more of the pharmaceutical layers comprises zonisamide, and at least one intermediate layer comprises a monosaccharide sugar, a disaccharide sugar or a starch. In another embodiment, one or more of the pharmaceutical layers comprises naltrexone, one or more of the pharmaceutical layers comprises fluoxetine, and at least one intermediate layer comprises a monosaccharide sugar, a disaccharide sugar or a starch.

In another embodiment, one or more of the pharmaceutical layers comprises olanzapine, one or more of the pharmaceutical layers comprises zonisamide, and at least one intermediate layer comprises a monosaccharide sugar, a disaccharide sugar or a starch. In another embodiment, one or more of the pharmaceutical layers comprises metformin, one or more of the pharmaceutical layers comprises zonisamide, and at least one intermediate layer comprises a monosaccharide sugar, a disaccharide sugar or a starch.

In another embodiment, one or more of the pharmaceutical layers comprises phentermine, one or more of the pharmaceutical layers comprises topiramate, and at least one intermediate layer comprises a monosaccharide sugar, a disaccharide sugar or a starch. In some embodiments the presence of one or more drugs in a pharmaceutical formulation enhances the desired physiological effects of the drugs over the additive physiological effects of the one or more drugs in comparable, but separate pharmaceutical formulations when administered alone.

In the illustrated embodiment, the fluid comprises at least one bodily fluid selected from saliva, sweat, chyme, mucus and bile. As the intermediate layer dissolves the pharmaceutical layers A and B begin to separate as shown. As noted above, in some embodiments each pharmaceutical layer comprises the same pharmaceutical composition. However, in the illustrated embodiment, the pharmaceutical layers A and B each comprise a different pharmaceutical composition.

In some embodiments, one or more of the pharmaceutical layers comprises a controlled-release formulation. In some embodiments, one or more of the controlled-release formulations comprises a sustained-release formulation. The pharmaceutical layers A and B have separated and remain substantially intact. The second pharmaceutical formulation comprises second pharmaceutical layers A, B and C. In some embodiments two or more of the second pharmaceutical layers A, B and C comprise the same pharmaceutical composition.

In the illustrated embodiment each of the pharmaceutical layers A, B and C comprises a different pharmaceutical composition. The second pharmaceutical formulation also comprises an intermediate layer configured to dissolve in vivo. The fluid, as represented by the arrow , has dissolved an intermediate layer and the second pharmaceutical layers A, B and C are separated and left substantially intact. The third pharmaceutical formulation comprises third pharmaceutical layers A, B and C separated by an intermediate layer Each of the third pharmaceutical layers A, B and C comprises one or more pharmaceutical compositions.

As illustrated in the third layered pharmaceutical formulation , the third pharmaceutical layer A comprises a similar dosage volume to the third pharmaceutical layer B. The third pharmaceutical layer C, however, comprises a larger dosage volume than third pharmaceutical layers A or B. As noted above with regard to FIG. The fourth pharmaceutical formulation includes, but is not limited to fourth pharmaceutical layers A and B and an intermediate layer The fourth pharmaceutical layer A comprises a first drug A and a second drug B.

The first drug A and the second drug B are positioned within the fourth pharmaceutical layer A so as to be in physical contact with the other; no intermediate layer separates the first drug A from the second drug B within the layer A. Similarly, the fourth pharmaceutical layer B comprises a third drug C and a fourth drug D; no intermediate layer separates the third drug C and the fourth drug D. In the fourth pharmaceutical formulation the intermediate layer is disposed between fourth pharmaceutical layers C and B.

In this embodiment, the edges of intermediate layer are not aligned with the fourth pharmaceutical layers C and B. A space allows for fluids to interact with and dissolve the intermediate layer Thus, although the intermediate layer is not flush with the outside edge of the fourth pharmaceutical formulation , the intermediate layer is exposed for purposes of dissolution upon contact with bodily fluids.

The fifth pharmaceutical formulation includes, but is not limited to fifth pharmaceutical layers A and B. The fifth pharmaceutical layers A and B each include, but are not limited to one or more pharmaceutical compositions. The fifth pharmaceutical formulation further comprises a first intermediate layer A and a second intermediate layer B. In some embodiments the first intermediate layer A is configured to physically and chemically separate the fifth pharmaceutical layers A and B.

In some embodiments the second intermediate layer B is configured to physically and chemically separate the fifth pharmaceutical layers A and B. The first intermediate layer A and the second intermediate layer B each comprise one or more formulations configured to dissolve in vivo. The sixth pharmaceutical formulation includes, but is not limited to sixth pharmaceutical layers A and B and an intermediate layer The sixth pharmaceutical formulation is configured in a lenticular shape, wherein each pharmaceutical layer A and B comprises a single convex shape.

Pharmaceutical layers may be configured in various shapes. For example, pharmaceutical layers may be configured in elliptical shapes, spherical shapes, oblong shapes, square shapes or flat shapes. In some embodiments pharmaceutical formulations are combined with fillers or excipients and placed in tablets, granules or capsules for later administration. In some embodiments the tablets are configured in spherical, elliptical, lenticular or capsule shapes.

The seventh pharmaceutical formulation includes, but is not limited to seventh pharmaceutical layers A, B, C, D, E and F. Each seventh pharmaceutical layer A, B, C, D, E and F comprises one or more pharmaceutical compositions. The seventh pharmaceutical formulation additionally comprises an intermediate layer disposed between seventh pharmaceutical layers B, C and D and also between seventh pharmaceutical layers A, F and E.

As described above the intermediate layer is configured to dissolve in vivo upon contact with a certain type of bodily fluid. The seventh pharmaceutical formulation additionally comprises a special intermediate layer disposed between seventh pharmaceutical layers A and B and between seventh pharmaceutical layers D and E. The special intermediate layer is configured to dissolve under bodily conditions different than those conditions that dissolve intermediate layer Upon dissolution of the special intermediate layer , the seventh pharmaceutical layers A and B and the seventh pharmaceutical layers D and E are left substantially intact.

For example, if intermediate layer were configured to dissolve under the acidic conditions of the stomach in a human patient, special intermediate layer may be configured to dissolve only after the pharmaceutical formulation reaches the duodenum. In some embodiments at least one of the pharmaceutical layers comprises an enteric coating. As noted above, pharmaceutical formulations may be configured in various shapes and sizes for ease of administration to a patient. Manufacture of pharmaceutical formulations configured in tablets comprises steps known in the art.

For example, tablets may be prepared through wet-granulation, dry-granulation or direct compression. Layered pharmaceutical formulations may be configured in tablet form in a similar manner. In some embodiments pharmaceutical formulations include, but are not limited to controlled-release formulations. In some embodiments the controlled-release formulations include, but are not limited to sustained-release formulations. In some embodiments the layered pharmaceutical formulation may be used to treat obesity.

Obesity is a disorder characterized by the accumulation of excess fat in the body. Obesity has been recognized as one of the leading causes of disease and is emerging as a global problem. Increased instances of complications from obesity, such as hypertension, non-insulin-dependent diabetes mellitus, arteriosclerosis, dyslipidemia, certain forms of cancer, sleep apnea and osteoarthritis, have been related to increased instances of obesity in the general population. Prior to , obesity was generally considered a psychological problem.

The discovery of the adipostatic hormone leptin in brought forth the realization that in certain cases, obesity may have a biochemical basis. The corollary to this realization was the idea that treatment of obesity may be achieved by chemical approaches. Since then, a number of such chemical treatments have entered the market. See, for example, U. Patent Application Publication Nos.

Other descriptions of bupropion, zonisamide, controlled-release zonisamide and combinations thereof are disclosed in U. Provisional Patent Application Nos. Even in controlled-release formulations, however, the administration of certain anticonvulsants or opioid receptor antagonists at a full dosage may initially incur severe adverse side effects. Thus, at least initially, patients may be unable to tolerate a full dosage of the prescribed drug, which may include, but is not limited to an anticonvulsant or an opioid receptor antagonist.

Administering combinations of drugs, for example, a combination including, but not limited to an anticonvulsant or an opioid receptor antagonist in combination with an antidepressant may enhance the ability of the anticonvulsant to affect weight loss, but does not necessarily eliminate the initial adverse side effects that may accompany the administration of the anticonvulsant or the opioid receptor antagonist.

In some embodiments a system comprises a layered pharmaceutical for minimizing side effects during treatment of obesity. In some embodiments a method comprises administering a layered pharmaceutical formulation comprising an anticonvulsant or the opioid receptor antagonist to affect weight loss while minimizing or eliminating the initial adverse side effects on the patient.

Some preferred embodiments comprise at least one of an antidepressant and an anticonvulsant. Other preferred embodiments comprise at least one of an antidepressant and an opioid receptor antagonist. Other preferred embodiments comprise at least one of an anticonvulsant and an opioid receptor antagonist. Other preferred embodiments comprise at least one of an anticonvulsant and an ant diabetic. In some embodiments an antidepressant comprises a dopamine reuptake inhibitor or receptor antagonist.

Examples of dopamine reuptake inhibitors include, but are not limited to phentermine and pharmaceutically acceptable salts or prodrugs thereof. Examples of dopamine receptor antagonists include, but are not limited to haloperidol, ocaperidone, risperidone, olanzapine, quetiapine, amisulpride, and pimozide and pharmaceutically acceptable salts or prodrugs thereof.

In some embodiments the antidepressant comprises a norepinephrine reuptake inhibitor. Examples of norepinephrine reuptake inhibitors include, but are not limited to bupropion, thionisoxetine, atomoxetine and reboxetine and pharmaceutically acceptable salts or prodrugs thereof. Other embodiments include, but are not limited to those in which the antidepressant is a dopamine agonist. Dopamine agonists available on the market include cabergoline, amantadine, lisuride, pergolide, ropinirole, pramipexole, and bromocriptine.

In some embodiments the antidepressant comprises a serotonin reuptake inhibitor. Examples of serotonin reuptake inhibitors include, but are not limited to fluoxetine and pharmaceutically acceptable salts or prodrugs thereof. Pharmaceutical salts can be obtained by reacting a compound of the disclosure with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like.

Pharmaceutical salts can also be obtained by reacting a compound of the disclosure with a base to form a salt such as ammonium salt, an alkali metal salt such as a sodium or a potassium salt, an alkaline earth metal salt such as a calcium or a magnesium salt, a salt of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, tris hydroxymethyl methylamine and salts thereof with amino acids such as arginine, lysine and the like. Prodrugs are often useful because, in some situations, they are easier to administer than the parent drug.

They can, for instance, be bioavailable by oral administration whereas the parent is not. The prodrug can also have improved solubility in pharmaceutical compositions over the parent drug or can demonstrate increased palpability or be easier to formulate. A further example of a prodrug might be a short peptide polyaminoacid bonded to an acid group where the peptide is metabolized to provide the active moiety.

The metabolites of bupropion suitable for inclusion in the methods and compositions described herein include the erythro- and threo-amino alcohols of bupropion, the erythro-amino diol of bupropion, and morpholinol metabolites of bupropion. The scope of the present disclosure includes the above-mentioned metabolites of bupropion as a free base or as a physiologically acceptable salt thereof. Controlled-release bupropion formulations of bupropion are known in the art.

Olanzapine, whose chemical name is 2-methyl 4-methylpiperazinyl H-thieno[2,3-b][1,5]benzodiazepine, is used as a psychotherapeutic agent primarily for the treatment of schizophrenia, acute manic episodes in bipolar disorder acute, maintenance treatment in bipolar disorder and agitation associated with both these disorders.

Olanzapine displays linear kinetics. Its elimination half-life ranges from 21 to 54 hours. Steady state plasma concentrations are achieved in about a week. Olanzapine undergoes extensive first pass metabolism and bioavailability is not affected by food. The psychotherapeutic agent may be selected from the group consisting of mirtazapine, setiptiline, paroxetine, venlafaxine, olanzapine, bupropion, risperidone, lamotrogine, risperidone, a lithium salt, valproic acid, and pharmaceutically acceptable salts or prodrugs thereof.

In some embodiments the psychotherapeutic agent is an antidepressant, an antimigrane, an antibipolar, an antimania drug, a mood stabilizer, or an antiepileptic. Examples of antidepressants include paroxetine, mirtazapine, and bupropion. Examples of antibipolar drugs include lithium, valproate, carbamezepine, oxycarbamezepine, lamotrogine, tiagabine, olanzapine, clozapine, risperidone, quetiapine, aripiprazole, ziprasidone, and benzodiazepines. Also included are pharmaceutically acceptable salts or prodrugs of these drugs, extended release or controlled release formulations of the above drugs, as well as combinations of the above drugs.

Fluoxetine is a selective serotonin reuptake inhibitor SSRI , whose chemical name is N-methylphenyl[4- trifluoromethyl phenoxy]-propanamine, is used primarily for the treatment of depression including pediatric depression , obsessive-compulsive disorder in both adult and pediatric populations , bulimia nervosa, panic disorder, premenstrual dysphoric disorder, hypochondriasis and body dysmorphic disorder.

It is highly bound to plasma proteins, mostly albumin. Its elimination half-life ranges from 1 to 3 days—after a single dose—to 4 to 6 days after long-term use in healthy adults, and is prolonged in those with liver disease. The half-life of norfluoxetine is longer 16 days after long-term use. Complete excretion of the drug may take several weeks.

The SSRI can be selected from fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram, sibutramine, duloxetine, and venlafaxine, and pharmaceutically acceptable salts or prodrugs thereof. In some embodiments, the SSRI is fluoxetine or a pharmaceutically acceptable salt or prodrug thereof.

Fluoxetine has a physiological half life of about 24 hours, whereas that of naltrexone is about 1. However their metabolites may demonstrate half-lives in excess of 24 hours. Thus, in some cases, it may be beneficial to administer one dose of fluoxetine per day in conjunction with two or three or more doses of naltrexone throughout the day. Naltrexone may also be in a time-release formulation where the dose is administered once a day, but naltrexone gradually enters the blood stream throughout the day, or in the course of a 12 hour period.

Symptoms of the obsessive compulsive disorders are inhibited in individuals being administered fluoxetine and naltrexone. Adverse events associated with the obsessive compulsive disorders are reduced in individuals being administered fluoxetine and naltrexone. The effects of administration of both fluoxetine and naltrexone on obsessive compulsive disorder are synergistic compared to effects of those expected by administration of fluoxetine and naltrexone alone.

Newer generation antidepressants include selective serotonin reuptake inhibitors e. Phentermine is an example of a dopamine reuptake inhibitor with a chemical name 2-methylphenylpropanamine and 2-methyl-amphetamine. In some embodiments an antidiabetic includes, but is not limited to a biguanide, glucosidase inhibitor, insulin, meglitinide, sulfonylurea or a thiazolidinedione. In some embodiments a biguanide comprises metformin hydrochloride. In some embodiments a glucosidase inhibitor includes, but is not limited to acarbose and miglitol.

Other examples of insulin include, but are not limited to mixtures of the various forms of insulin e. NPH and regular human and pork insulin. Insulin may be from Saccharomyces cerevisiae or other sources. Examples of meglitinides include, but are not limited to nateglinide and repaglinide. Examples of sulfonylureas include, but are not limited to glimepiride, glyburide, glibenclamide, gliquidone, gliclazide, chlorpropamide, tolbutamide, tolazamide and glipizide.

Examples of thiazolidinediones include, but are not limited to rosiglitazone and pioglitazone. Also included are extended release formulations of the above drugs, as well as combinations of the above drugs and pharmaceutically acceptable salts or prodrugs thereof. As mentioned above, in certain embodiments, the antidiabetic is metformin.

Metformin, whose chemical name is 1- diaminomethylidene -3,3-dimethyl-guanidine, is often used in the treatment of diabetes mellitus type 2, especially when accompanied obesity and insulin resistance. Metformin has also been proven to reduce the cardiovascular complications of diabetes. In some embodiments, the anticonvulsant is selected from the group including, but not limited to zonisamide, topiramate, nembutal, lorazepam, clonazepam, clorazepate, tiagabine, gabapentin, fosphenytoin, phenytoin, carbamazepine, balproate, felbamate, lebetiracetam, oxcarbazepine, lamotrigine, methsuximide and ethosuxmide.

Zonisamide is a marketed anticonvulsant indicated as adjunctive therapy for adults with partial onset seizures. Without being bound by any particular theory, it is believed that the mechanism of antiepileptic activity appears to be: Further, zonisamide facilitates serotonergic and dopaminergic neurotransmission and possesses a weak inhibitory effect on carbonic anhydrase.

Zonisamide has been shown to cause significant weight loss comparable to marketed weight loss medications in patients presenting primary obesity. It has been postulated that the affect of zonisamide on the CNS concentration of serotonin, dopamine and carbonic anhydrase is responsible for this effect. There is evidence that zonisamide increases serotonin and dopamine synthesis rates herein. There is further evidence suggesting that zonisamide stimulates dopamine D 2 receptors. Zonisamide can be formulated in a controlled- or sustained-release tablet or gel form.

This allows a patient newly prescribed zonisamide to ramp up the dosage level over a period of several days. This increase in dosage form allows the patient to avoid some of the negative side effects that have been exhibited during the initial administration of zonisamide to a patient. Some of these initial side effects include a shock to the body. Although patients who start with a full dose of zonisamide will become acclimated to the dosage over a period of time, the negative side effects accompanying the initial shock to the body can be avoided with a method wherein dosages are increased over a period of several days.

Although the exact dosages will be determined on a drug-by-drug basis, in most cases some generalizations regarding the dosage can be made. Some descriptions of appropriate unit dosages of drugs including, but not limited to bupropion, zonisamide, controlled-release zonisamide and combinations thereof are disclosed in U. Provisional Patent Application No. In some embodiments, the GABA inhibitor is topiramate.

Topiramate, whose chemical name is 2,3: Generally, initial doses of topiramate are low and increased in slow steps. The usual initial dose is 25 to 50 mg daily in 2 single doses. Recommended increments vary, but are usually between 25 mg and 50 mg every 1 or 2 weeks. Common doses for maintenance treatment include, but are not limited to doses of approximately to mg daily.

The mammal may be selected from the group including, but not limited to mice, rats, rabbits, guinea pigs, dogs, cats, sheep, goats, cows, primates, such as monkeys, chimpanzees, and apes, and humans. In some embodiments the opioid antagonist is selected from the group including, but not limited to alvimopan, norbinaltorphimine, nalmefene, naloxone, naltrexone, methylnaltrexone, and nalorphine, and pharmaceutically acceptable salts or prodrugs thereof.

In other embodiments, the opioid antagonist is a partial opioid agonist. Compounds of this class have some agonist activity at opioid receptors. However, because they are weak agonists, they function as de-facto antagonists. Examples of partial opioid agonists include, but are not limited to pentacozine, buprenorphine, nalorphine, propiram, and lofexidine.

CNS Drugs , 10, The maximum serum concentration of immediate release naltrexone is reached very rapidly, typically a T max of approximately 1 hour. Immediate release naltrexone can induce side effects such as nausea, which is attributable to the maximum blood plasma concentration levels C max. An oral dosage form of naltrexone that is able to effect naltrexone release at a rate sufficiently slow to ameliorate side effects, yet sufficiently fast to achieve good bioavailability would provide a significant improvement in dosing compliance and convenience.

Likewise, an improved dosage form which lowered the incidence of gastrointestinal side-effects would also be of significant value. Formulations of controlled- or sustained-release naltrexone have been disclosed in U. Those skilled in the art informed by the guidance provided herein can formulate oral dosage forms described herein.

Below are found specific examples of pharmaceutical compositions that may be formed into layered pharmaceutical formulations of the present disclosure. Vege- table Source Grade G Thus, as illustrated in Tables above, embodiments of pharmaceutical formulations may comprise controlled-release e. In one embodiment, a layered pharmaceutical formulation is a tablet comprising a first layer comprising a controlled-release zonisamide and a second layer comprising a bupropion. In another embodiment a layered pharmaceutical formulation is a tablet comprising a first layer comprising a controlled-release naltrexone and a second layer comprising a controlled-release bupropion.

In some embodiments the first layer and the second layer are separated by an intermediate layer comprising lactose or other suitable fast-dissolving ingredient. The oral dosage forms of pharmaceutical formulations can, if desired, be presented in a unit dosage package which may contain one or more unit dosage forms containing the active ingredient.

The unit dosage package may for example comprise metal or plastic foil, such as a blister pack. The unit dosage package may be accompanied by instructions for administration. The unit dosage package may also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration.

Such notice, for example, may be the labeling approved by the U. Food and Drug Administration for prescription drugs, or the approved product insert. Compositions comprising a compound of the disclosure formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. In some embodiments, the weight loss medications are provided at least once, twice or three times a day for a set period, which can be at least, at least about, less than, less than about, equal to or between any range within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 consecutive days or at least, at least about, less than, less than about, equal to or between any range within of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 consecutive weeks or at least, at least about, less than, less than about, equal to or between any range within 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 consecutive months.

The amount of drug in any pharmaceutical formulation described herein includes, but is not limited to amounts of at least, at least about, less than, less than about, equal to or between any range within 0. In one embodiment a layered pharmaceutical formulation for the administration of two or more active pharmaceutical ingredients comprises a first pharmaceutical layer comprising a first active pharmaceutical ingredient, a second pharmaceutical layer comprising a second active pharmaceutical ingredient and at least one intermediate layer disposed between the first and the second pharmaceutical layers, wherein the at least one intermediate layer is configured to dissolve in vivo to thereby leave the first and the second pharmaceutical layers substantially intact.

In some embodiments each of the first and the second pharmaceutical layers comprises a dissolution profile substantially similar to a singularly compressed tablet of a similar composition. In some embodiments each of the first and the second pharmaceutical layers comprises a different pharmaceutical composition. In some embodiments at least one of the first and the second pharmaceutical layers comprises a controlled-release pharmaceutical composition.

In some embodiments the controlled-release pharmaceutical composition comprises a sustained release pharmaceutical composition. In some embodiments at least one of the first and the second pharmaceutical layers comprises zonisamide. In some embodiments the zonisamide comprises a controlled-release zonisamide. In some embodiments the controlled-release zonisamide comprises a sustained-release zonisamide.

In some embodiments at least one of the first and the second pharmaceutical layers comprises bupropion. In some embodiments the bupropion comprises a controlled-release bupropion. In some embodiments the controlled-release bupropion comprises a sustained-release bupropion. In some embodiments at least one of the first and the second pharmaceutical layers comprises naltrexone. In some embodiments at least one of the first and the second pharmaceutical layers comprises fluoxetine.

In some embodiments at least one of the first and the second pharmaceutical layers comprises olanzapine. In some embodiments at least one of the first and the second pharmaceutical layers comprises an antidiabetic. In some embodiments the antidiabetic comprises metformin. In some embodiments at least one of the first and the second pharmaceutical layers comprises topiramate.

In some embodiments at least one of the first and the second pharmaceutical layers comprises phentermine. In some embodiments the at least one intermediate layer comprises at least one of a monosaccharide sugar, a disaccharide sugar, or a starch. In some embodiments the at least one intermediate layer comprises lactose. In some embodiments the first dosage is greater than the second dosage.

In some embodiments the second dosage is greater than the first dosage. In one embodiment a method for treating an obesity related condition in a patient comprises identifying a patient with an obesity related condition or at risk of an obesity related condition comprises providing a first dosage of the layered pharmaceutical formulation of claims 1 to the patient on a first day and providing a second dosage of the layered pharmaceutical formulation to the patient on a second day.

In some embodiments the first dosage is different than the second dosage. In one embodiment use of a first compound and a second compound in the formulation of a medicament for affecting weight loss, suppressing appetite or treating an obesity-related condition, wherein the medicament comprises a layered pharmaceutical formulation of the present invention. It will be appreciated by those skilled in the art that various modifications and changes can be made without departing from the scope of the disclosure.

Such modifications and changes are intended to fall within the scope of the disclosure, as defined by the appended claims. Year of fee payment: In one embodiment a layered pharmaceutical formulation includes two or more pharmaceutical layers and an intermediate layer disposed between at least two of the two or more pharmaceutical layers, the intermediate layer configured to dissolve in vivo to thereby leave the two or more pharmaceutical layers substantially intact.

In one embodiment, an active pharmaceutical ingredient in at least one of the pharmaceutical layers is selected from bupropion, zonisamide, naltrexone, topiramate, phentermine, metformin, olanzapine and fluoxetine. Description of the Related Art Certain types of layered tablets are known in pharmaceutical applications. SUMMARY An embodiment provides a layered pharmaceutical formulation comprising two or more pharmaceutical layers and an intermediate layer disposed between at least two of the two or more pharmaceutical layers.

Manufacture of Pharmaceutical Formulations As noted above, pharmaceutical formulations may be configured in various shapes and sizes for ease of administration to a patient. Pharmaceutical Formulations to Treat Obesity In some embodiments the layered pharmaceutical formulation may be used to treat obesity. Antidepressants and Psychotherapeutics In some embodiments an antidepressant comprises a dopamine reuptake inhibitor or receptor antagonist.

Antidiabetic In some embodiments an antidiabetic includes, but is not limited to a biguanide, glucosidase inhibitor, insulin, meglitinide, sulfonylurea or a thiazolidinedione.

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