DRUG INTERACTIONS-   

1.Effect of Other Drugs on SEYSARA Oral Retinoids- Tetracyclines may cause increased intracranial pressure as do oral retinoids, including isotretinoin and acitretin.

 Avoid coadministration of SEYSARA with oral retinoids.

 Antacids and Iron Preparations- Coadministration with antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron containing preparations may impair absorption of SEYSARA, similar to other tetracyclines, which may decrease its efficacy. Separate dosing of SEYSARA from antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron-containing preparations.

 2. Effect of SEYSARA on Other Drugs-                                                                           Penicillin -Similar to other tetracycline, SEYSARA may interfere with the bactericidal action of penicillin. Avoid coadministration of SEYSARA with penicillin.

 Anticoagulants -Similar to other tetracyclines, SEYSARA may depress plasma prothrombin activity, which may increase the risk of bleeding in patients who are on anticoagulant therapy. Decrease anticoagulant dosage when coadministered with SEYSARA as appropriate.

 P-Glycoprotein (P-gp) Substrates- Concomitant use of SEYSARA may increase concentrations of concomitantly administered P-gp substrates (e.g. digoxin). Monitor for toxicities of drugs that are P-gp substrates and may require dosage reduction when given concurrently with SEYSARA.

 Oral Hormonal Contraceptives-                                                                                       There is no clinically significant effect of SEYSARA on the efficacy of oral contraceptives containing ethinyl estradiol and norethindrone acetate.

BRIEF SUMMARY

SERECYCLINE- (Oct 2018)

Indn-         To treat inflammatory lesions of non-nodular moderate to severe  vulgaris in patients 9 years of age and older       

Comp-     Tablets: 60 mg, 100 mg, 150 mg .It  is a tetracycline-class drug indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older.  

Limitations of Use- Efficacy of  beyond 12 weeks and safety beyond 12 months have not been established.  has not been evaluated in the treatment of infections.

ADR-     Most common adverse reaction (incidence = 1%) is nausea.

CI-    is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines. 

WARNINGS -

 • The use of  during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown).

• If Clostridium difficile Associated Diarrhea (antibiotic associated colitis) occurs, discontinue        

Pat Inform-

Patients taking  should receive the following information and instructions:

 • SEYSARA should not be used by pregnant women or women attempting to conceive a child • Advise a woman that breast feeding is not recommended during SEYSARA therapy.

==============================================================

U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  42

ADVERSE REACTIONS-

 Most common adverse reaction (incidence = 1%) is nausea.

CONTRAINDICATIONS-

 SEYSARA is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines. 

WARNINGS AND PRECAUTIONS-

 • The use of SEYSARA during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown).

• If Clostridium difficile Associated Diarrhea (antibiotic associated colitis) occurs, discontinue SEYSARA                                                                                                         • Central nervous system side effects, including light-headedness, dizziness or vertigo, have been reported with tetracycline use. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery. These symptoms may disappear during therapy and may disappear when the drug is discontinued.                                                                                                                         • SEYSARA may cause intracranial hypertension. Discontinue SEYSARA if symptoms occur.                                                                                                                                      • Photosensitivity can occur with SEYSARA. Patients should minimize or avoid exposure to natural or artificial sunlight.

  PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Patient Information).

 Patients taking SEYSARA should receive the following information and instructions:

 • SEYSARA should not be used by pregnant women or women attempting to conceive a child 

• Advise a woman that breast feeding is not recommended during SEYSARA therapy.

• Advise patients that C. difficile colitis can occur with antibiotic therapy. If patients develop watery or bloody stools, they should seek medical attention. 

 • Advise patients that intracranial hypertension can occur with tetracycline therapy. If patients experience headache or blurred vision, they should seek medical attention.

• Patients who experience central nervous system symptoms should be cautioned about driving vehicles or using hazardous machinery while on SEYSARA therapy. Patients should seek medical help for persistent central nervous system symptoms.

• Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Advise patients to minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using SEYSARA. If patients need to be outdoors while using SEYSARA, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. Treatment should be discontinued at the first evidence of skin erythema.

 • Advise patients that because of the potential for drug-resistant bacteria to develop during the use of SEYSARA, take SEYSARA as directed. Skipping doses or not completing the full course of therapy may decrease the effectiveness of the current treatment course and increase the likelihood that bacteria will develop resistance and will not be treatable by other antibacterial drugs in the future.

 • Advise patients to drink fluids liberally along with SEYSARA to reduce the risk of esophageal irritation and ulceration 

© 2018 Allergan. All rights reserved. SEYSARA™ is a trademark of Allergan Pharmaceuticals International Limited. Allergan® and its design are trademarks of Allergan, Inc.

Distributed by: Allergan USA, Inc. Madison, NJ 07940 USA  

  CLINICAL PHARMACOLOGY-

1.  Mechanism of Action-                                                                                                The mechanism of action of SEYSARA in treating acne vulgaris is not known.

2. Pharmacodynamics-                                                                                                      The pharmacodynamics of SEYSARA for the treatment of acne vulgaris are unknown. 

 Cardiac Electrophysiology- At approximately 3 times the maximum recommended dose, SEYSARA did not prolong the QT interval to a clinically relevant extent.

3.  Pharmacokinetics-                                                                                                         Increasing the SEYSARA dose from 60 to 150 mg once daily in healthy subjects resulted in a slightly less than proportional increase in sarcyeline steady-state Cmax and AUCtau. A mean accumulation ratio of sarecycline ranges from 1.5 to 1.6 fold with repeated dosing. Steady-state of sarecycline was reached by Day 7.

 Absorption-                                                                                                                       The median time to peak plasma concentration (Tmax) of sarecycline is 1.5 to 2.0 hours. 

 Effect of Food-                                                                                                                  Coadministration with a high-fat (approximately 50% of total caloric content of the  meal), high-calorie (800 to 1000 Kcal) meal that included milk delayed Tmax by approximately 0.53 hour and decreased sarecycline Cmax by 31% and AUC by 27%. 

 Distribution-                                                                                                                      Protein binding of sarecycline is 62.5% to 74.7% in vitro. The mean apparent volume of distribution of sarecycline at steady-state ranges from 91.4 L to 97.0 L.  

Elimination-                                                                                                                         The mean apparent oral clearance (CL/F) of sarecycline at steady state is approximately 3 L/h. The mean elimination half-life of sarecycline is 21 to 22 hours.

 Metabolism-                                                                                                                       Metabolism of sarecycline by enzymes in human liver microsomes is minimal (< 15%) in vitro. Minor metabolites resulting from non-enzymic epimerization, O-/N-demethylation, hydroxylation, and desaturation have been found.

 Excretion-                                                                                                                       After a single 100 mg oral dose of radiolabeled sarecycline, 42.6% of the dose was recovered in feces (14.9% as unchanged) and 44.1% in urine (24.7% as unchanged).  

Specific Populations-

 No clinically significant differences in the pharmacokinetics of sarecycline were observed based on age (11 to 73 years), weight (42 to 133 kg), sex, renal impairment, or mild to moderate hepatic impairment (Child Pugh A to B). The effect of end-stage renal disease (ESRD) or severe hepatic impairment (Child-Pugh C) on sarecycline pharmacokinetics has not been assessed.  

 Drug Interaction Studies-

 Clinical Studies-                                                                                                                  Coadministration of SEYSARA with a combination oral contraceptive, ethinyl estradiol (EE) 20 mcg plus norethindrone (NE) acetate 1 mg, increased EE Cmax by 14% and AUCtau by 11%, and increased NE Cmax by 18% and AUCtau by 23%. 

Coadministration of a single dose of SEYSARA 150 mg resulted in a 26% increase in Cmax of digoxin, a P-gp substrate.

  USE IN SPECIFIC POPULATIONS-

1.Pregnancy -Risk Summary-                                                                                            SEYSARA, like tetracycline class drugs, may cause fetal harm, permanent discoloration of teeth, and reversible inhibition of bone growth when administered during pregnancy.                                                                                                                                             The limited available human data are not sufficient to inform a drugassociated risk for birth defects or miscarriage.

 Tetracyclines are known to cross the placental barrier; therefore, SEYSARA may be transmitted from the mother to the developing fetus.        

 All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 

2. Lactation Risk-  Summary-                                                                                             Tetracyclines are excreted in human milk. Because of the potential for serious adverse reactions on bone and tooth development in nursing infants from tetracycline-class antibiotics, advise a woman that breastfeeding is not recommended with SEYSARA therapy 

3. Females and Males of Reproductive Potential Infertility-                                            Avoid using SEYSARA in males who are attempting to conceive a child. In a fertility study in rats, sarecycline adversely affected spermatogenesis when orally administered to male rats at a dose 8 times the MRHD (based on AUC comparison)

4.   Pediatric Use-                                                                                                                The safety and effectiveness of SEYSARA have been established in pediatric patients 9 years of age and older for the treatment of moderate to severe inflammatory lesions of non-nodular acne vulgaris.

 Safety and effectiveness of SEYSARA in pediatric patients below the age of 9 years has not been established. Use of tetracycline-class antibiotics below the age of 8 is not recommended due to the potential for tooth discoloration 

5.  Geriatric Use-                                                                                                                Clinical studies of SEYSARA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 

 OVERDOSAGE-                                                                                                                 In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdose.