Melzara

Drug overview for MELZARA (azelaic acid/tranexamic acid/niacinamide):

Generic name: AZELAIC ACID/TRANEXAMIC ACID/NIACINAMIDE
Drug class: Acne Products
Therapeutic class: Dermatological

No enhanced Introduction information available for this drug.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for MELZARA (azelaic acid/tranexamic acid/niacinamide) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following drug interaction information is available for MELZARA (azelaic acid/tranexamic acid/niacinamide):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 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
Antifibrinolytics/Factor IX; Anti-Inhibitor Coagulant Conc SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use may result in additive or synergistic effects on the coagulation pathways.(1-3) CLINICAL EFFECTS: Concurrent use may result in thrombosis.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates.(1) The US manufacturer of tranexamic acid states that concomitant use with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates should be avoided.(2,3) The Japanese manufacturer of tranexamic acid recommends caution when coadministered with drugs such as coagulation factor agents as coagulation may be further activated at sites with enhanced local fibrinolysis.(4) Concurrent use may be warranted in select patients with hemophilia A or hemophilia B or in select major trauma scenarios. Monitor patients closely for signs of thrombosis, disseminated intravascular coagulation, and hypercoagulability if concurrent use is deemed necessary.(5-13) DISCUSSION: There is very limited data on the risk of thrombosis with combination therapy. In a study, eight hemophilia B patients undergoing dental extraction procedures received combination therapy with aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX for bleeding prophylaxis. All patients achieved hemostasis without clinical evidence of thrombosis as well as no changes were seen in hemoglobin, hematocrit, or in markers of hemostatic system activation.(5) In a study, seven hemophilia A patients with inhibitors and one with acquired hemophilia patient received activated prothrombin complex concentrate (APCC) and tranexamic acid for management of bleeding episodes and prevention of hemorrhage during surgery. Hemostatic outcomes were rated excellent or good in 10 out of 11 (91%) treatment episodes. No episodes of thrombosis or disseminated intravascular coagulation occurred during treatment.(6) A study in six hemophilia A patients and five healthy volunteers evaluated the use of tranexamic acid as an adjunct to APCC to control bleeding. Patients who received tranexamic acid had a significant increase in maximum clot firmness compared to healthy controls. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed.(7) In a retrospective cohort of 76 patients who received PCC for bleeding not caused by anticoagulation, some patients received additional hemostatic agents (protamine (59%), desmopressin (43%), and tranexamic acid (42%). Eight patients (11%) suffered thromboembolic complications but this was not stratified by the hemostatic agent.(8) In a prospective case crossover study, five healthy volunteers and six hemophilia patients with inhibitors received tranexamic acid with single-dose activated PCC or with recombinant activated factor VII. There were no thromboembolic events during the study.(9) In a double-blind, randomized, placebo-controlled superiority trial to investigate the efficacy and safety of 4-factor prothrombin complex concentrate (4F-PCC) administration in trauma patients at risk of massive transfusion, a significantly higher risk of thromboembolic events occurred in the 4F-PCC group compared to the placebo group (35% vs 24%; relative risk 1.48 [95% CI, 1.04-2.10]). This was observed despite more frequent use of tranexamic acid in the placebo group (86% vs 76%).(10) Case reports reviewed the use of recombinant factor VIIa and FEIBA in 4 patients with severe hemophilia with inhibitors who underwent major surgery. The patients were also treated with tranexamic acid. Non-surgical bleeding was encountered in 4 of 8 surgical procedures. The overall outcome was good for all procedures.(11) In a retrospective cohort of 112 ambulatory tooth extractions in 23 hemophilia patients using a coagulation factor replacement therapy in combination with tranexamic acid, only one episode of mild postoperative bleeding occurred after seven days in a patient who did not have good treatment compliance.(12) In a prospective study evaluating the use of initial hemoglobin levels as a guideline for the initial treatment of clotting disorders in multiple trauma patients, 25 patients received a combination of hemostatic agents (fibrinogen (100%), PCC (96%), desmopressin (56%), tranexamic acid (52%), and factor VIIa (44%). Of the 25 patients treated, 16 (64%) survived. Two patients (8%) suffered thromboembolic complications but this was not stratified by the hemostatic agent. One patient survived after developing a grade II pulmonary embolism caused by deep leg vein trombosis and one patient died from multi-organ failure after developing multiple small vessel thrombosis.(13)	ALPHANINE SD, ALPROLIX, BENEFIX, FEIBA, IDELVION, IXINITY, KCENTRA, PROFILNINE, REBINYN, RIXUBIS

Drug Interaction

Drug Names

Antifibrinolytics/Factor IX; Anti-Inhibitor Coagulant Conc

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use may result in additive or synergistic effects on the coagulation pathways.(1-3)

CLINICAL EFFECTS: Concurrent use may result in thrombosis.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates.(1) The US manufacturer of tranexamic acid states that concomitant use with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates should be avoided.(2,3) The Japanese manufacturer of tranexamic acid recommends caution when coadministered with drugs such as coagulation factor agents as coagulation may be further activated at sites with enhanced local fibrinolysis.(4)

Concurrent use may be warranted in select patients with hemophilia A or hemophilia B or in select major trauma scenarios. Monitor patients closely for signs of thrombosis, disseminated intravascular coagulation, and hypercoagulability if concurrent use is deemed necessary.(5-13)

DISCUSSION: There is very limited data on the risk of thrombosis with combination therapy. In a study, eight hemophilia B patients undergoing dental extraction procedures received combination therapy with aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX for bleeding prophylaxis. All patients achieved hemostasis without clinical evidence of thrombosis as well as no changes were seen in hemoglobin, hematocrit, or in markers of hemostatic system activation.(5)

In a study, seven hemophilia A patients with inhibitors and one with acquired hemophilia patient received activated prothrombin complex concentrate (APCC) and tranexamic acid for management of bleeding episodes and prevention of hemorrhage during surgery. Hemostatic outcomes were rated excellent or good in 10 out of 11 (91%) treatment episodes. No episodes of thrombosis or disseminated intravascular coagulation occurred during treatment.(6)

A study in six hemophilia A patients and five healthy volunteers evaluated the use of tranexamic acid as an adjunct to APCC to control bleeding. Patients who received tranexamic acid had a significant increase in maximum clot firmness compared to healthy controls. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed.(7)

In a retrospective cohort of 76 patients who received PCC for bleeding not caused by anticoagulation, some patients received additional hemostatic agents (protamine (59%), desmopressin (43%), and tranexamic acid (42%). Eight patients (11%) suffered thromboembolic complications but this was not stratified by the hemostatic agent.(8) In a prospective case crossover study, five healthy volunteers and six hemophilia patients with inhibitors received tranexamic acid with single-dose activated PCC or with recombinant activated factor VII.

There were no thromboembolic events during the study.(9) In a double-blind, randomized, placebo-controlled superiority trial to investigate the efficacy and safety of 4-factor prothrombin complex concentrate (4F-PCC) administration in trauma patients at risk of massive transfusion, a significantly higher risk of thromboembolic events occurred in the 4F-PCC group compared to the placebo group (35% vs 24%; relative risk 1.48 [95% CI, 1.04-2.10]). This was observed despite more frequent use of tranexamic acid in the placebo group (86% vs 76%).(10)

Case reports reviewed the use of recombinant factor VIIa and FEIBA in 4 patients with severe hemophilia with inhibitors who underwent major surgery. The patients were also treated with tranexamic acid. Non-surgical bleeding was encountered in 4 of 8 surgical procedures.

The overall outcome was good for all procedures.(11) In a retrospective cohort of 112 ambulatory tooth extractions in 23 hemophilia patients using a coagulation factor replacement therapy in combination with tranexamic acid, only one episode of mild postoperative bleeding occurred after seven days in a patient who did not have good treatment compliance.(12) In a prospective study evaluating the use of initial hemoglobin levels as a guideline for the initial treatment of clotting disorders in multiple trauma patients, 25 patients received a combination of hemostatic agents (fibrinogen (100%), PCC (96%), desmopressin (56%), tranexamic acid (52%), and factor VIIa (44%).

Of the 25 patients treated, 16 (64%) survived. Two patients (8%) suffered thromboembolic complications but this was not stratified by the hemostatic agent. One patient survived after developing a grade II pulmonary embolism caused by deep leg vein trombosis and one patient died from multi-organ failure after developing multiple small vessel thrombosis.(13)

ALPHANINE SD, ALPROLIX, BENEFIX, FEIBA, IDELVION, IXINITY, KCENTRA, PROFILNINE, REBINYN, RIXUBIS

There are 0 moderate interactions.

Moderate List
Asthma
No disease contraindications

The following adverse reaction information is available for MELZARA (azelaic acid/tranexamic acid/niacinamide):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 5 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Angioedema Asthma exacerbation Dyspnea Urticaria Wheezing

There are 15 less severe adverse reactions.

More Frequent	Less Frequent
Dry skin Erythema Paresthesia Pruritus of skin Skin inflammation Stinging of skin	None.

Rare/Very Rare
Abnormal desquamation Application site rash Facial edema Hirsutism Ocular irritation Periorbital edema Recurrent herpes simplex labialis Skin hypopigmentation Vitiligo

The following precautions are available for MELZARA (azelaic acid/tranexamic acid/niacinamide):

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.