Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Sarecycline belongs to the pharmacological class of Tetracycline antibiotics.
Sarecycline has been approved to relieve symptoms and also for the treatment and maintenance of Acne vulgaris.
After oral administration, sarecycline is rapidly absorbed with a time to maximum concentration (Tmax) of 2-4 hours and a peak plasma concentration (Cmax) that is dose-proportional over the recommended dosage range of 60-150 mg/day. The bioavailability of sarecycline is reduced by approximately 38% when taken with a high-fat meal. The drug has a relatively long elimination half-life of approximately 12-16 hours, allowing for once-daily dosing. Sarecycline is primarily eliminated via the fecal route, with only a small portion being excreted in the urine.
The common side effects involved in using Sarecycline are Diarrhea, Nausea, Vomiting, Abdominal pain, Headache, Dizziness, Rash, discoloration of teeth , nails and gums and Itching.
Sarecycline is available in the form of Tablets.
Sarecycline is approved in Germany, Japan, Malaysia, India, the U.K., the U.S, and China.
Sarecycline belongs to the pharmacological class of Tetracycline antibiotics.
Sarecycline's mechanism of action is thought to involve the inhibition of various macromolecular biosynthesis processes, such as microbial DNA, RNA, protein, lipid, and cell wall biosynthesis . Specifically, it has been observed that sarecycline has a notable impact on the inhibition of microbial DNA and protein synthesis, while having little to no effect on lipid biosynthesis, cell wall synthesis, and RNA synthesis . Moreover, Cutibacterium acnes also produces proteins and enzymes that are capable of inducing inflammation, and it is suggested that tetracyclines like sarecycline may have an anti-inflammatory effect by inhibiting such microbial protein synthesis .
Sarecycline has been approved to relieve symptoms and also for the treatment and maintenance of Acne vulgaris.
The maximum concentration of sarecycline in the blood is reached approximately 2 to 4 hours after oral administration of a single dose.The time to reach Cmax is approximately 2 to 4 hours after oral administration of a single dose.
The onset of action of sarecycline is not well defined. The half-life of sarecycline is approximately 16 hours. It is typically dosed once daily for 12 weeks in the treatment of acne vulgaris.
Sarecycline is found to be available in the form of Tablets.
Sarecycline can be used in the following treatment:
- Acne vulgaris
Sarecycline can help to relieve symptoms and also for the treatment and maintenance of Acne vulgaris.
Sarecycline is approved for use in the following clinical indications:
- Acne vulgaris
For moderate to severe inflammatory acne vulgaris, it is recommended to use this medication in combination with topical acne therapy. To minimize the risk of resistance, the treatment should not exceed 3 to 4 months ideally. The recommended oral dosage varies based on the patient's body weight, with 60 mg once daily for those weighing 33 to 54 kg, 100 mg once daily for those weighing 55 to 84 kg, and 150 mg once daily for those weighing 85 to 136 kg.
Tablets: 60mg, 100mg, 150mg.
Tablets
- Dosage Adjustments in Kidney Patients:
The manufacturer's labeling does not include specific dosage adjustments, so caution is advised along with a potential adjustment in dosage and/or time interval between doses. Hemodialysis or peritoneal dialysis are not effective methods for removing tetracyclines in significant amounts.
- Dosage Adjustments in Pediatric Patients:
Treatment for Moderate to Severe Non-Nodular Acne Vulgaris
For children aged 9 years and above as well as adolescents, the following oral doses are recommended for moderate to severe non-nodular acne vulgaris. If there is no improvement observed after 12 weeks of treatment, reassessment of the treatment plan is necessary.
- Patients weighing 33 to less than 55 kg: 60 mg once daily
- Patients weighing 55 to less than 85 kg: 100 mg once daily
- Patients weighing 85 to 136 kg: 150 mg once daily
In the case of C. trachomatis or U. urealyticum
- Infections, 100 mg PO is given every 12 hours for 7 days.
In general, for infections,
- The dosing for Sarecycline is not recommended for children below 8 years of age unless
● Other antibiotics are not an option. For children 8 years and above, the initial dose is 4 mg/kg PO/IV, not to exceed 200 mg, followed by a maintenance dose of 2 mg/kg PO/IV every 12 hours, not to exceed the adult dose. The recommended dose is not to exceed 100 mg PO/IV every 12 hours for 5-10 days.
There are no specific dietary restrictions related to the use of Sarecycline. However, like with most antibiotics, it is generally recommended to take Sarecycline with a full glass of water and to avoid taking it with milk or other dairy products as they may decrease the absorption of the medication. Additionally, taking Sarecycline with food can help minimize the risk of gastrointestinal upset.
Sarecycline may be contraindicated under the following conditions:
- Patients who have a known hypersensitivity to any component of Sarecycline or to other drugs in the same class.
The physician should closely monitor the patients and keep pharmacovigilance as follows:
- Teratogenic Effects
A. Fetal Harm: Sarecycline and other tetracyclines can harm a developing fetus, and pregnant women should be informed of this risk. Treatment should be immediately stopped if Sarecycline is used during pregnancy or if the patient becomes pregnant while taking Sarecycline.
B. Tooth Discoloration: The use of tetracycline-class drugs during tooth development may cause permanent discoloration of teeth. This adverse reaction is more common during long-term use but has been observed following repeated short-term courses.
C. Skeletal Development: Tetracyclines form a stable calcium complex in bone-forming tissue, and animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development in the fetus. Sarecycline use during pregnancy has been associated with embryotoxicity in animals.
- CDAD: Clostridium difficile associated diarrhea (CDAD) may occur with nearly all antibacterial agents, including Sarecycline, and may range in severity from mild diarrhea to fatal colitis. Antibiotic use alters the normal flora of the colon leading to potential overgrowth of C. difficile.
- CNS Effects: 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.
- Intracranial Hypertension: Tetracyclines, including Sarecycline, have been associated with intracranial hypertension in adults and adolescents. Women of childbearing age who are overweight have a greater risk for developing intracranial hypertension. Patients should be checked for papilledema if visual disturbances occur during treatment.
- Photosensitivity: Photosensitivity, manifested by an exaggerated sunburn reaction, has been observed in some individuals taking tetracyclines. Patients should minimize or avoid exposure to natural or artificial sunlight while using Sarecycline.
- Development of Drug Resistant Bacteria: Bacterial resistance to tetracyclines may develop in patients using Sarecycline. It should only be used as indicated.
- Superinfection/Potential for Microbial Overgrowth: Use of Sarecycline may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, Sarecycline should be discontinued and appropriate therapy instituted.
Alcohol Warning
There is no specific alcohol warning associated with the use of Sarecycline. However, it is generally recommended to avoid excessive alcohol consumption while taking antibiotics as it can interfere with the effectiveness of the medication and may also increase the risk of certain side effects such as nausea, vomiting, and dizziness.
Breast Feeding Warning
As tetracyclines are excreted in human milk, there is a risk of significant adverse effects on the development of bones and teeth in nursing infants when using tetracycline-class antibiotics, including Sarecycline. Therefore, it is recommended that women avoid breastfeeding while undergoing Sarecycline therapy.
Pregnancy Warning
Pregnancy Category D:
Sarecycline, a tetracycline class drug, has the potential to cause fetal harm, permanent tooth discoloration, and reversible inhibition of bone growth if administered during pregnancy, as stated in Warnings and Precautions and Use in Specific Populations. However, the limited human data available are inadequate to determine the potential risk for drug-associated birth defects or miscarriage. As tetracyclines are known to cross the placenta, Sarecycline may be passed from the mother to the developing fetus. Studies conducted on pregnant rats revealed that administering sarecycline orally during organogenesis at a dose of 1.4 times the maximum recommended human dose (MRHD) of 150 mg/day (based on AUC comparison) resulted in fetal skeletal malformations. When the dose was increased to three times the MRHD (based on AUC comparison) and continued through lactation, there were reductions in offspring survival, body weight, implantation sites, and viable embryos in offspring females. The potential risk to the fetus outweighs the potential benefit to the mother from Sarecycline use during pregnancy; therefore, pregnant patients should discontinue Sarecycline as soon as pregnancy is recognized.
All pregnancies carry a risk of birth defects, loss, or other adverse outcomes. However, the estimated background risk of major birth defects and miscarriage in the indicated population is unknown. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Food Warning
Sarecycline oral should be taken with caution or avoided with dairy products, calcium supplements, iron supplements, magnesium supplements, zinc supplements, and antacids containing aluminum, magnesium, or calcium, as these can bind to Sarecycline and reduce its absorption from the gastrointestinal tract. This can lead to reduced effectiveness of the medication. To avoid this interaction, Sarecycline should be taken at least 2 hours before or after these products.
The adverse reactions related to Sarecycline can be categorized as follows:
Common:
- Nausea
- Vomiting
- Dizziness
- Diarrhea
- Headache
- Skin rash
- Pruritus (itching)
- Abdominal pain
- Hypertension (high blood pressure)
- Phlebitis (inflammation of a vein)
Less Common:
- Anorexia (loss of appetite)
- Photosensitivity (increased sensitivity to sunlight)
- Asthenia (weakness or lack of energy)
- Dyspnea (shortness of breath)
- Chest pain
- Tachycardia (rapid heart rate)
- Arthralgia (joint pain)
- Myalgia (muscle pain)
- Hyperpigmentation (excess pigmentation of the skin)
- Urinary tract infection
Rare:
- Hypersensitivity reactions (e.g. anaphylaxis, angioedema)
- Hepatotoxicity (liver damage)
- Renal failure
- Blood dyscrasias (abnormalities in blood cell counts)
- Intracranial hypertension (increased pressure inside the skull)
The clinically relevant drug interactions of Sarecycline are briefly summarized here:
Effect of Other Drugs on Sarecycline:
- Oral Retinoids: Sarecycline should not be taken with oral retinoids, as both may cause increased intracranial pressure.
- Antacids and Iron Preparations: Taking Sarecycline with antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, or iron-containing preparations may impair its absorption and decrease its efficacy. To avoid this, separate dosing of Sarecycline from antacids and iron preparations.
- Penicillin: Sarecycline may interfere with the bactericidal action of penicillin. Avoid coadministration of Sarecycline with penicillin.
- Anticoagulants: Sarecycline 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 Sarecycline as appropriate.
- P-Glycoprotein (P-gp) Substrates: Concomitant use of Sarecycline 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 Sarecycline.
Effect of Sarecycline on Other Drugs:
- Oral Hormonal Contraceptives: Sarecycline does not significantly affect the efficacy of oral contraceptives containing ethinyl estradiol and norethindrone acetate.
The following are the side effects involving Sarecycline:
- Nausea and vomiting
- Dizziness
- Headache
- Rash
- Diarrhea
- Discoloration of skin, teeth, nails, or gums
- Yeast infections
Pregnancy:
Pregnancy Category D:
Sarecycline, a tetracycline class drug, has the potential to cause fetal harm, permanent tooth discoloration, and reversible inhibition of bone growth if administered during pregnancy, as stated in Warnings and Precautions and Use in Specific Populations. However, the limited human data available are inadequate to determine the potential risk for drug-associated birth defects or miscarriage. As tetracyclines are known to cross the placenta, Sarecycline may be passed from the mother to the developing fetus. Studies conducted on pregnant rats revealed that administering sarecycline orally during organogenesis at a dose of 1.4 times the maximum recommended human dose (MRHD) of 150 mg/day (based on AUC comparison) resulted in fetal skeletal malformations. When the dose was increased to three times the MRHD (based on AUC comparison) and continued through lactation, there were reductions in offspring survival, body weight, implantation sites, and viable embryos in offspring females. The potential risk to the fetus outweighs the potential benefit to the mother from Sarecycline use during pregnancy; therefore, pregnant patients should discontinue Sarecycline as soon as pregnancy is recognized.
All pregnancies carry a risk of birth defects, loss, or other adverse outcomes. However, the estimated background risk of major birth defects and miscarriage in the indicated population is unknown. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Nursing Mothers
As tetracyclines are excreted in human milk, there is a risk of significant adverse effects on the development of bones and teeth in nursing infants when using tetracycline-class antibiotics, including Sarecycline. Therefore, it is recommended that women avoid breastfeeding while undergoing Sarecycline therapy.
Pediatric Use
Sarecycline has been found to be safe and effective for treating moderate to severe inflammatory lesions of non-nodular acne vulgaris in pediatric patients aged 9 years and older, as demonstrated in pharmacokinetic and clinical studies. However, there is no evidence to support the safety and efficacy of Sarecycline in pediatric patients under the age of 9. It is not advisable to use tetracycline-class antibiotics in children below the age of 8 due to the risk of tooth discoloration.
Geriatric Use
There were not enough participants aged 65 and above in clinical trials of Sarecycline to establish whether they have a different response to the medication compared to younger individuals.
Physicians should be knowledgeable as well as vigilant about the treatment and identification of over dosage of Sarecycline.
If an overdose occurs, the medication should be discontinued, and symptoms should be treated accordingly, while also providing supportive care. Dialysis is not effective in treating cases of overdose as it does not affect the serum half-life of the drug.
Pharmacodynamics
Compared to first-line tetracycline therapies such as doxycycline and Sarecycline for treating moderate to severe acne, studies suggest that sarecycline has significantly lower activity (sixteen to thirty-two fold) against aerobic Gram-negative bacilli found in the human intestinal microbiome. Additionally, sarecycline has been shown to be four to eight fold less active against various anaerobic bacteria also present in the human intestinal microbiome. In contrast, doxycycline and Sarecycline exhibit broad-spectrum antimicrobial activity, which may lead to adverse effects such as diarrhea, fungal overgrowth, and vaginal candidiasis due to their off-target antibacterial effects on endogenous intestinal flora. Sarecycline, on the other hand, has a more targeted and narrow spectrum of activity, resulting in a lower incidence of such side effects. Furthermore, sarecycline has a relatively low propensity for resistance development in Cutibacterium acnes, one of the primary anaerobic organisms associated with acne lesions, which is similar to doxycycline and Sarecycline treatments.
Pharmacokinetics
- Absorption:
Sarecycline reaches its maximum plasma concentration (Tmax) within 1.5 to 2.0 hours.
- Effect of Food:
The administration of sarecycline with a high-fat and high-calorie meal that included milk resulted in a delay of approximately 0.53 hour to Tmax and a decrease in sarecycline's maximum concentration (Cmax) by 31% and area under the curve (AUC) by 27%.
- Distribution:
In vitro studies show that sarecycline has a protein binding of 62.5% to 74.7%. At steady-state, the mean apparent volume of distribution of sarecycline ranges from 91.4 L to 97.0 L.
- Elimination:
At steady state, the mean apparent oral clearance (CL/F) of sarecycline is approximately 3 L/h. The elimination half-life of sarecycline ranges from 21 to 22 hours.
- Metabolism:
In vitro studies show that sarecycline is minimally metabolized by enzymes in human liver microsomes (< 15%). However, minor metabolites resulting from non-enzymic epimerization, O-/N-demethylation, hydroxylation, and desaturation have been identified.
- Excretion:
Following a single 100 mg oral dose of radiolabeled sarecycline, approximately 42.6% of the dose was recovered in feces (14.9% as unchanged) and 44.1% in urine (24.7% as unchanged).
- https://www.mayoclinic.org/drugs-supplements/sarecycline-oral-route/side-effects/drg-20444050?p=1
- https://www.webmd.com/drugs/2/drug-176237/sarecycline-oral/details
- https://go.drugbank.com/drugs/DB12035
- https://my.clevelandclinic.org/health/drugs/21309-sarecycline-oral-tablets
- https://reference.medscape.com/drug/Sarecycline-sarecycline-1000228
- https://www.drugs.com/mtm/sarecycline.html
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209521s007lbl.pdf
- https://www.mayoclinic.org/drugs-supplements/sarecycline-oral-route/side-effects/drg-20444050?p=1
- https://www.webmd.com/drugs/2/drug-176237/sarecycline-oral/details
- https://go.drugbank.com/drugs/DB12035
- https://my.clevelandclinic.org/health/drugs/21309-sarecycline-oral-tablets
- https://reference.medscape.com/drug/Sarecycline-sarecycline-1000228
- https://www.drugs.com/mtm/sarecycline.html
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209521s007lbl.pdf
