Eb-A7 Dr

Drug overview for EB-A7 DR (s-adenosylmeth/collagen/hyaluronic/boswellia/turmeric/pepper):

Generic name: s-adenosylmeth/collagen/hyaluronic/Boswellia/turmeric/pepper
Drug class:
Therapeutic class: Alternative Therapy

No enhanced Introduction information available for this drug.

No enhanced Uses information available for this drug.

DRUG IMAGES

No Image Available

The following indications for EB-A7 DR (s-adenosylmeth/collagen/hyaluronic/boswellia/turmeric/pepper) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following drug interaction information is available for EB-A7 DR (s-adenosylmeth/collagen/hyaluronic/boswellia/turmeric/pepper):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
S-Adenosylmethionine (SAM-e)/Tranylcypromine SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: S-adenosylmethionine (SAMe), and tranylcypromine are suggested to have similar effects on the serotonin pathway, therefore their use together may result in additive or synergistic effects. CLINICAL EFFECTS: Concomitant use of S-adenosylmethionine and antidepressants which inhibit neuronal serotonin reuptake may result in serotonin syndrome. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of tranylcypromine states that concurrent use of S-adenosylmethionine and tranylcypromine is contraindicated.(1) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: There is a case report with a tricyclic antidepressant (clomipramine) and tranylcypromine of serotonin syndrome. Tricyclic antidepressants are also known to increase serotonin levels.(2)	PARNATE, TRANYLCYPROMINE SULFATE

Drug Interaction

Drug Names

S-Adenosylmethionine (SAM-e)/Tranylcypromine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: S-adenosylmethionine (SAMe), and tranylcypromine are suggested to have similar effects on the serotonin pathway, therefore their use together may result in additive or synergistic effects.

CLINICAL EFFECTS: Concomitant use of S-adenosylmethionine and antidepressants which inhibit neuronal serotonin reuptake may result in serotonin syndrome. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of tranylcypromine states that concurrent use of S-adenosylmethionine and tranylcypromine is contraindicated.(1) If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea.

DISCUSSION: There is a case report with a tricyclic antidepressant (clomipramine) and tranylcypromine of serotonin syndrome. Tricyclic antidepressants are also known to increase serotonin levels.(2)

PARNATE, TRANYLCYPROMINE SULFATE

There are 4 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Selected Chemotherapy Agents/Turmeric (Curcumin) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Curcumin, the major component of turmeric, has been shown to decrease chemotherapy-induced apoptosis by inhibition of reactive oxygen species generation and blockade of the c-Jun NH2-terminal kinase pathway.(1) CLINICAL EFFECTS: Concurrent use of turmeric (curcumin) may decrease the effectiveness of some chemotherapy agents.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving cytotoxic therapy for breast cancer should be excluded from curcumin-based chemotherapy.(1) It would be prudent to instruct patients to avoid or limit consumption of curcumin or turmeric. DISCUSSION: In vitro studies in MCF-7 cancer cell lines showed that curcumin decreased camptothecin-induced, doxorubicin-induced, and mechlorethamine-induced apoptosis. In vivo tests in mice xenograft models of human breast cancer, dietary curcumin decreased cyclophosphamide-induced tumor regression.(1)	ADRIAMYCIN, CAELYX, CAMPTOSAR, CYCLOPHOSPHAMIDE, CYCLOPHOSPHAMIDE MONOHYDRATE, DOXIL, DOXORUBICIN HCL, DOXORUBICIN HCL LIPOSOME, FRINDOVYX, IRINOTECAN HCL, MECHLORETHAMINE HCL, ONIVYDE
Pazopanib/Selected Inhibitors of P-gp or BCRP SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of pazopanib.(1) CLINICAL EFFECTS: The concurrent administration of pazopanib with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of pazopanib and signs of toxicity.(1) PREDISPOSING FACTORS: The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The US manufacturer of pazopanib states concurrent use of P-gp inhibitors or BCRP inhibitors should be avoided.(1) Monitor patients for increased side effects from pazopanib. If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: Pazopanib is a substrate of P-gp and BCRP. Inhibitors of these transporters are expected to increase pazopanib levels.(1) BCRP inhibitors linked to this monograph include: asciminib, belumosudil, clopidogrel, cyclosporine, curcumin, darolutamide, eltrombopag, enasidenib, febuxostat, fostemsavir, grazoprevir, lazertinib, leflunomide, leniolisib, momelotinib, oteseconazole, pantoprazole, pirtobrutinib, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, teriflunomide, tolvaptan, turmeric, and vadadustat.(1,3-5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, capmatinib, carvedilol, cyclosporine, danicopan, daridorexant, diltiazem, flibanserin, fostamatinib, ginseng, glecaprevir/pibrentasvir, isavuconazonium, ivacaftor, ledipasvir, neratinib, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, tezacaftor, ticagrelor, valbenazine, verapamil, vimseltinib, and voclosporin.(3,4)	PAZOPANIB HCL, VOTRIENT
Cladribine/Selected Inhibitors of BCRP SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of BCRP may increase the absorption of cladribine.(1-2) CLINICAL EFFECTS: The concurrent administration of cladribine with an inhibitor of BCRP may result in elevated levels of cladribine and signs of toxicity.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of cladribine states concurrent use of BCRP inhibitors should be avoided during the 4- to 5-day cladribine treatment.(1-2) Selection of an alternative concurrent medication with no or minimal transporter inhibiting proprieties should be considered. If this is not possible, dose reduction to the minimum mandatory dose of the BCRP inhibitor, separation in timing of administration, and careful patient monitoring is recommended.(1-2) Monitor for signs of hematologic toxicity. Lymphocyte counts should be monitored. DISCUSSION: Cladribine is a substrate of BCRP. Inhibitors of this transporter are expected to increase cladribine levels.(1-2) BCRP inhibitors linked to this monograph include: capmatinib, clopidogrel, curcumin, danicopan, darolutamide, dasabuvir, eltrombopag, enasidenib, febuxostat, fostamatinib, fostemsavir, glecaprevir/pibrentasvir, grazoprevir, lazertinib, oteseconazole, pacritinib, pantoprazole, paritaprevir, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, selpercatinib, sofosbuvir/velpatasvir/voxilaprevir, tafamidis, ticagrelor, tolvaptan, turmeric, and vadadustat.(1-4)	CLADRIBINE, MAVENCLAD
Topotecan/BCRP Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of the BCRP transporter may increase the intestinal absorption and hepatic uptake of topotecan.(1) CLINICAL EFFECTS: The concurrent administration of topotecan with an inhibitor of BCRP may result in elevated levels of topotecan and signs of toxicity. These signs may include but are not limited to anemia, diarrhea, and thrombocytopenia.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of topotecan states that the use of topotecan and BCRP inhibitors should be avoided. If concurrent use is warranted, carefully monitor patients for adverse effects.(1) DISCUSSION: In clinical studies, the combined use of elacridar (100 mg to 1000 mg), a BCRP and P-gp inhibitor, increased the area-under-curve (AUC) of topotecan approximately 2.5-fold.(1) BCRP inhibitors linked to this monograph include: capmatinib, clopidogrel, curcumin, danicopan, dasabuvir, elbasvir, enasidenib, febuxostat, fostamatinib, fostemsavir, glecaprevir, grazoprevir, lazertinib, oteseconazole, pacritinib, pantoprazole, paritaprevir, pibrentasvir, pirtobrutinib, regorafenib, resmetirom, ritonavir, roxadustat, tafamidis, ticagrelor, tolvaptan, turmeric, vadadustat, velpatasvir, and voxilaprevir.(2,3)	HYCAMTIN, TOPOTECAN HCL

There are 2 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Ubrogepant/P-gp or BCRP Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of ubrogepant.(1) CLINICAL EFFECTS: The concurrent administration of ubrogepant with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of ubrogepant.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with P-gp or BCRP inhibitors. The dose of ubrogepant should not exceed 50 mg for initial dose. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(1) The manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to ubrogepant.(3) DISCUSSION: Ubrogepant is a substrate of P-gp and BCRP transporters. Use of P-gp or BCRP inhibitors may increase the exposure of ubrogepant. Clinical drug interaction studies with inhibitors of these transporters were not conducted. The US manufacturer of ubrogepant recommends dose adjustment if ubrogepant is coadministered with P-gp or BCRP inhibitors.(1) BCRP inhibitors linked to this monograph include: belumosudil, clopidogrel, curcumin, eltrombopag, febuxostat, fostemsavir, leniolisib, momelotinib, oteseconazole, pantoprazole, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, oral tedizolid, turmeric, and vadadustat.(2-5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, carvedilol, danicopan, daridorexant, neratinib, osimertinib, propafenone, quinidine, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, tezacaftor, valbenazine, vimseltinib, and voclosporin.(2-5)	UBRELVY
Atorvastatin; Rosuvastatin/Selected BCRP Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Atorvastatin and rosuvastatin are both substrates of the BCRP transporter.(1-3) Inhibitors of this transporter may increase intestinal absorption and hepatic uptake of BCRP substrates atorvastatin and rosuvastatin.(1-9) CLINICAL EFFECTS: Simultaneous use of BCRP inhibitors may result in increased levels and side effects from atorvastatin and rosuvastatin, including rhabdomyolysis.(1,3,5) PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. Patients on rosuvastatin with ABCG2 polymorphisms leading to decreased or poor BCRP transporter function may have increased rosuvastatin concentrations and risk of myopathy. PATIENT MANAGEMENT: Concurrent use may result in increased risk of side effects associated with atorvastatin and rosuvastatin. If concurrent therapy is warranted, close monitoring would be prudent for statin related side effects including rhabdomyolysis. The Canadian manufacturer of clopidogrel states that the dose of rosuvastatin should not exceed 20 mg daily when used concomitantly with clopidogrel.(6) There is no recommendation for rosuvastatin dose adjustments from the Australian and US manufacturers of clopidogrel.(7,8) Educate the patient of signs and symptoms of rhabdomyolysis. DISCUSSION: Atorvastatin and rosuvastatin are both BCRP substrates.(1-3) In a clinical study of 20 patients with stable coronary heart disease, single-dose clopidogrel 300 mg increased the area-under-curve (AUC) and maximum concentration (Cmax) of rosuvastatin by 2-fold and 1.3-fold, respectively. Multiple doses of clopidogrel 75 mg daily for 7 days increased rosuvastatin AUC by 1.4-fold but did not affect the Cmax.(5) In a pharmacokinetic study, concomitant use of lazertinib increased rosuvastatin Cmax by 2.2-fold and AUC by 2-fold.(4) BCRP inhibitors include: clopidogrel, curcumin, encorafenib, lazertinib, pacritinib, pantoprazole, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, tolvaptan, and turmeric.(3-9)	AMLODIPINE-ATORVASTATIN, ATORVALIQ, ATORVASTATIN CALCIUM, CADUET, CRESTOR, EZALLOR SPRINKLE, LIPITOR, ROSUVASTATIN CALCIUM, ROSUVASTATIN-EZETIMIBE, ROSZET

Drug Interaction

Drug Names

Ubrogepant/P-gp or BCRP Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Inhibitors of P-glycoprotein (P-gp) or BCRP may increase the absorption of ubrogepant.(1)

CLINICAL EFFECTS: The concurrent administration of ubrogepant with an inhibitor of P-glycoprotein or BCRP may result in elevated levels of ubrogepant.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with P-gp or BCRP inhibitors. The dose of ubrogepant should not exceed 50 mg for initial dose. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(1)

The manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to ubrogepant.(3)

DISCUSSION: Ubrogepant is a substrate of P-gp and BCRP transporters. Use of P-gp or BCRP inhibitors may increase the exposure of ubrogepant. Clinical drug interaction studies with inhibitors of these transporters were not conducted.

The US manufacturer of ubrogepant recommends dose adjustment if ubrogepant is coadministered with P-gp or BCRP inhibitors.(1) BCRP inhibitors linked to this monograph include: belumosudil, clopidogrel, curcumin, eltrombopag, febuxostat, fostemsavir, leniolisib, momelotinib, oteseconazole, pantoprazole, regorafenib, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, oral tedizolid, turmeric, and vadadustat.(2-5) P-glycoprotein inhibitors linked to this monograph include: asunaprevir, belumosudil, carvedilol, danicopan, daridorexant, neratinib, osimertinib, propafenone, quinidine, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, tezacaftor, valbenazine, vimseltinib, and voclosporin.(2-5)

UBRELVY

Atorvastatin; Rosuvastatin/Selected BCRP Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Atorvastatin and rosuvastatin are both substrates of the BCRP transporter.(1-3) Inhibitors of this transporter may increase intestinal absorption and hepatic uptake of BCRP substrates atorvastatin and rosuvastatin.(1-9)

CLINICAL EFFECTS: Simultaneous use of BCRP inhibitors may result in increased levels and side effects from atorvastatin and rosuvastatin, including rhabdomyolysis.(1,3,5)

PREDISPOSING FACTORS: The risk for myopathy or rhabdomyolysis may be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. Patients on rosuvastatin with ABCG2 polymorphisms leading to decreased or poor BCRP transporter function may have increased rosuvastatin concentrations and risk of myopathy.

PATIENT MANAGEMENT: Concurrent use may result in increased risk of side effects associated with atorvastatin and rosuvastatin. If concurrent therapy is warranted, close monitoring would be prudent for statin related side effects including rhabdomyolysis. The Canadian manufacturer of clopidogrel states that the dose of rosuvastatin should not exceed 20 mg daily when used concomitantly with clopidogrel.(6)

There is no recommendation for rosuvastatin dose adjustments from the Australian and US manufacturers of clopidogrel.(7,8) Educate the patient of signs and symptoms of rhabdomyolysis.

DISCUSSION: Atorvastatin and rosuvastatin are both BCRP substrates.(1-3) In a clinical study of 20 patients with stable coronary heart disease, single-dose clopidogrel 300 mg increased the area-under-curve (AUC) and maximum concentration (Cmax) of rosuvastatin by 2-fold and 1.3-fold, respectively.

Multiple doses of clopidogrel 75 mg daily for 7 days increased rosuvastatin AUC by 1.4-fold but did not affect the Cmax.(5) In a pharmacokinetic study, concomitant use of lazertinib increased rosuvastatin Cmax by 2.2-fold

and AUC by 2-fold.(4) BCRP inhibitors include: clopidogrel, curcumin, encorafenib, lazertinib, pacritinib, pantoprazole, resmetirom, ritonavir, rolapitant, roxadustat, tafamidis, tolvaptan, and turmeric.(3-9)

AMLODIPINE-ATORVASTATIN, ATORVALIQ, ATORVASTATIN CALCIUM, CADUET, CRESTOR, EZALLOR SPRINKLE, LIPITOR, ROSUVASTATIN CALCIUM, ROSUVASTATIN-EZETIMIBE, ROSZET

Contraindication List
Biliary calculus
Gallbladder disease

Moderate List
Disease of liver
Gastroesophageal reflux disease

The following adverse reaction information is available for EB-A7 DR (s-adenosylmeth/collagen/hyaluronic/boswellia/turmeric/pepper):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 1 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Drug-induced hepatitis

There are 13 less severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Abdominal distension Abdominal pain with cramps Constipation Diarrhea Dyspepsia Flatulence Gastritis Gastroesophageal reflux disease Nausea Pruritus of skin Tongue discoloration Urticaria Vomiting

The following precautions are available for EB-A7 DR (s-adenosylmeth/collagen/hyaluronic/boswellia/turmeric/pepper):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

No enhanced Pregnancy information available for this drug.

No enhanced Lactation information available for this drug.

No enhanced Geriatric Use information available for this drug.