Acnestar Gel

Acnestar Gel (Acnestar Gel palmitate HCl) is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria.

Acnestar Gel is also indicated in the treatment of serious infections due to susceptible strains of streptococci, pneumococci and staphylococci. Its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgment of the physician, a penicillin is inappropriate. Because of the risk of colitis, as described in the WARNING box, before selecting Acnestar Gel the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).

Anaerobes: Serious respiratory tract infections such as empyema, anaerobic pneumonitis and lung abscess; serious skin and soft tissue infections; septicemia; intra-abdominal infections such as peritonitis and intra-abdominal abscess (typically resulting from anaerobic organisms resident in the normal gastrointestinal tract); infections of the female pelvis and genital tract such as endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis and postsurgical vaginal cuff infection.

Streptococci: Serious respiratory tract infections; serious skin and soft tissue infections.

Staphylococci: Serious respiratory tract infections; serious skin and soft tissue infections.

Pneumococci: Serious respiratory tract infections.

Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to Acnestar Gel.

In Vitro Susceptibility Testing

A standardized disk testing procedure2 is recommended for determining susceptibility of aerobic bacteria to Acnestar Gel. A description is contained in the CLEOCIN® Susceptibility Disk (Acnestar Gel) insert. Using this method, the laboratory can designate isolates as resistant, intermediate, or susceptible. Tube or agar dilution methods may be used for both anaerobic and aerobic bacteria. When the directions in the CLEOCIN® Susceptibility Powder insert are followed, an MIC (minimal inhibitory concentration) of 1.6 mcg/mL may be considered susceptible; MICs of 1.6 to 4.8 mcg/mL may be considered intermediate and MICs greater than 4.8 mcg/mL may be considered resistant.

CLEOCIN Susceptibility Disks 2 mcg. See package insert for use.

CLEOCIN Susceptibility Powder 20 mg. See package insert for use.

For anaerobic bacteria the minimal inhibitory concentration (MIC) of Acnestar Gel can be determined by agar dilution and broth dilution (including microdilution) techniques. If MICs are not determined routinely, the disk broth method is recommended for routine use. THE KIRBY-BAUER DISK DIFFUSION METHOD AND ITS INTERPRETIVE STANDARDS ARE NOT RECOMMENDED FOR ANAEROBES.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Acnestar Gel and other antibacterial drugs, Acnestar Gel should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Acnestar Gel belongs to the family of medicines called antibiotics.

Topical Acnestar Gel is used to help control acne. It may be used alone or with one or more other medicines that are used on the skin or taken by mouth for acne.

Topical Acnestar Gel may also be used for other problems as determined by your doctor.

Acnestar Gel is available only with your doctor's prescription.

Acnestar Gel phosphate IM administration should be used undiluted.

Acnestar Gel phosphate IV administration should be diluted.

Adults: Acnestar Gel phosphate (IM or IV administration): The usual daily adult dosage of Acnestar Gel phosphate for infections of the intraabdominal area, female pelvis, and other complicated or serious infections is 2400-2700 mg given in 2, 3, or 4 equal doses. Less complicated infections due to more susceptible microorganisms may respond to lower doses such as 1200-1800 mg/day administered in 3 or 4 equal doses.

Doses of up to 4800 mg daily have been used successfully.

Single IM doses of greater than 600 mg are not recommended.

Acnestar Gel hydrochloride capsules (oral administration): 600-1800 mg/day divided in 2, 3 or 4 equal doses. To avoid the possibility of esophageal irritation, Acnestar Gel HCl capsules should be taken with a full glass of water.

Children (>1 month): Acnestar Gel phosphate (IM or IV administration): 20-40 mg/kg/day in 3 or 4 equal doses.

Acnestar Gel hydrochloride capsules or Acnestar Gel palmitate solution (oral administration): To avoid the possibility of esophageal irritation, Acnestar Gel HCl capsules should be taken with a full glass of water. Doses of 8-25 mg/kg/day in 3 or 4 equal doses. In children weighing ≤10 kg, ½ teaspoon (37.5 mg) of Acnestar Gel palmitate solution three times a day should be considered the minimum recommended dose.

Neonates (<1 month): Acnestar Gel phosphate (IM or IV administration): 15-20 mg/kg/day in 3 or 4 equal doses. The lower dosage may be adequate for small premature infants.

Elderly: Pharmacokinetic studies with Acnestar Gel have shown no clinically important differences between young and elderly subjects with normal hepatic function and normal (age-adjusted) renal function after oral or intravenous administration. Therefore, dosage adjustments are not necessary in the elderly with normal hepatic function and normal (age-adjusted) renal function.

Renal Impairment: Acnestar Gel dosage modification is not necessary in patients with renal insufficiency.

Hepatic Impairment: Acnestar Gel dosage modification is not necessary in patients with hepatic insufficiency.

Specific

Indications:

Inpatient Treatment of Pelvic Inflammatory Disease: Acnestar Gel phosphate 900 mg (IV) every 8 hrs daily plus an antibiotic with an appropriate gram negative aerobic spectrum administered IV, eg, gentamicin 2 mg/kg followed by 1.5 mg/kg every 8 hrs daily in patients with normal renal function. Continue (IV) drugs for at least 4 days and at least 48 hrs after the patient improves. Then continue oral Acnestar Gel hydrochloride 450-600 mg q6h daily to complete 10-14 days total therapy. Treatment of Chlamydia trachomatis Cervicitis: Acnestar Gel hydrochloride capsules orally 450-600 mg 4 times daily for 10-14 days.

Treatment of Toxoplasmic Encephalitis in Patients with AIDS: Acnestar Gel phosphate IV or Acnestar Gel hydrochloride orally 600-1200 mg every 6 hrs for 2 weeks followed by 300-600 mg orally every 6 hrs. The usual total duration of therapy is 8 to 10 weeks. The dose of pyrimethamine is 25 to 75 mg orally each day for 8 to 10 weeks. Folinic acid 10 to 20 mg/day should be given with higher doses of pyrimethamine.

Treatment of Pneumocystis carinii Pneumonia in Patients with AIDS: Acnestar Gel phosphate IV 600 to 900 mg every 6 hrs or 900 mg IV every 8 hrs or Acnestar Gel hydrochloride 300 to 450 mg orally every 6 hrs for 21 days and Primaquine 15 to 30 mg dose orally once daily for 21 days. Treatment of Acute Streptococcal Tonsillitis/Pharyngitis: Acnestar Gel hydrochloride capsules 300 mg orally twice daily for 10 days.

Treatment of Malaria: Acnestar Gel hydrochloride capsules or Acnestar Gel palmitate solution (oral administration).

Uncomplicated Malaria/P. falciparum: Adults: Quinine sulfate: 650 mg orally three times daily for 3 or 7 days plus Acnestar Gel: 20 mg base/kg/day orally divided three times daily for 7 days. Children: Quinine sulfate: 10 mg/kg orally three times daily for 3 or 7 days plus Acnestar Gel: 20 mg base/kg/day orally divided three times daily for 7 days.

Severe Malaria: Adults: Quinidine gluconate: 10 mg/kg loading dose IV over 1-2 hrs, then 0.02 mg/kg/min continuous infusion for at least 24 hrs (for alternative dosing regimen please refer to quinidine label). Once parasite density <1% and patient can take oral medication, complete treatment with oral quinine, dose as above, plus Acnestar Gel: 20 mg base/kg/day orally divided three times daily for 7 days. If patient not able to take oral medication, give 10 mg base/kg Acnestar Gel loading dose IV followed by 5 mg base/kg IV every 8 hrs. Avoid rapid IV administration. Switch to oral Acnestar Gel (oral dose as above) as soon as patient can take oral medication. Treatment course=7 days.

Children: Quinidine gluconate: Same mg/kg dosing and recommendations as for adults plus Acnestar Gel: 20 mg base/kg/day orally divided three times daily for 7 days. If patient not able to take oral medication, give 10 mg base/kg Acnestar Gel loading dose IV followed by 5 mg base/kg IV every 8 hrs. Avoid rapid IV administration. Switch to oral Acnestar Gel (oral dose as above) as soon as patient can take oral medication. Treatment course=7 days.

Prophylaxis of Endocarditis in Patients Sensitive to Penicillin: Acnestar Gel hydrochloride capsules or Acnestar Gel palmitate solution (oral administration).

Adults: 600 mg 1 hr before procedure; children: 20 mg/kg 1 hr before procedure. Alternatively, when parenteral administration is required: Acnestar Gel phosphate 600 mg IV 1 hr before procedure. Prophylaxis of Infection in Head and Neck Surgery: Acnestar Gel phosphate 900 mg diluted in 1000 mL normal saline for use as an intraoperative irrigant in contaminated head and neck surgery prior to wound closure.

Dilution and IV Infusion Rates: The concentration of Acnestar Gel in diluent for infusion should not exceed 18 mg/mL and infusion rates should not exceed 30 mg per minute. The usual infusion rates are as follows:.

Administration of >1200 mg in a single 1-hr infusion is not recommended.

See also:
What is the most important information I should know about Acnestar Gel?

Acnestar Gel® Vaginal Cream, is contraindicated in individuals with a history of hypersensitivity to Acnestar Gel, lincomycin, or any of the components of this vaginal cream. Acnestar Gel® Vaginal Cream, is also contraindicated in individuals with a history of regional enteritis, ulcerative colitis, or a history of "antibiotic-associated" colitis.

Use Acnestar Gel cream as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Acnestar Gel cream is for vaginal use only.
• Wash your hands before and after using Acnestar Gel cream. To use, remove the cap from the tube. Screw the plastic applicator on the threaded end of the tube. Rolling the tube from the bottom, squeeze gently and force the medicine into the applicator. The applicator is filled when the plunger reaches its predetermined stopping point.
• Unscrew the applicator from the tube and replace the cap. While lying on your back, firmly grasp the applicator barrel and insert into the vagina as far as it will possibly go without causing discomfort. Slowly push the plunger until it stops. Carefully remove the applicator from the vagina and throw the applicator away.
• Use Acnestar Gel cream at bedtime. This will help keep the medicine in the vagina and reduce leaking.
• Acnestar Gel cream works best if it is used at the same time each day.
• To clear up your infection completely, use Acnestar Gel cream for the full course of treatment. Keep using it even if you feel better in a few days.
• If you miss a dose of Acnestar Gel cream and you are using it regularly, use it as soon as possible. If several hours have passed or if it is nearing time for the next dose, do not double the dose to catch up, unless advised by your health care provider. Do not use 2 doses at once. If more than one dose is missed, contact your doctor or pharmacist.

Ask your health care provider any questions you may have about how to use Acnestar Gel cream.

Use: Labeled Indications

Bone and joint infections: Treatment of bone and joint infections, including acute hematogenous osteomyelitis caused by Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections caused by susceptible organisms.

Gynecological infections: Treatment of gynecologic infections, including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes.

Intraabdominal infections: Treatment of intraabdominal infections, including peritonitis and intraabdominal abscess caused by susceptible anaerobic organisms.

Lower respiratory tract infections: Treatment of lower respiratory tract infections, including pneumonia, empyema, and lung abscess caused by susceptible anaerobes, Streptococcus pneumoniae, other streptococci (except Enterococcus faecalis), and S. aureus.

Septicemia: Treatment of septicemia caused by S. aureus, streptococci (except E. faecalis), and susceptible anaerobes.

Skin and soft tissue infection: Treatment of skin and soft tissue infection caused by Streptococcus pyogenes, S. aureus, and susceptible anaerobes.

Off Label Uses

Anthrax

Based on the Centers for Disease Control and Prevention (CDC) expert panel meetings on prevention and treatment of anthrax in adults, Acnestar Gel is an effective and acceptable alternative for postexposure prophylaxis or treatment of cutaneous anthrax; it is also a first-line option, in combination with other antimicrobials, for the treatment of systemic anthrax. Alternative regimens have also been suggested for other patient populations with anthrax, including injectable drug users who develop injectional anthrax.

Streptococcal (group A) pharyngitis and chronic carriage

Based on the IDSA guidelines for the diagnosis and management of group A streptococcal pharyngitis, Acnestar Gel is an effective and recommended alternative agent for the treatment of streptococcal pharyngitis and an option for treatment of chronic group A streptococcal carriage.

Surgical prophylaxis

Based on the American Society of Health-System Pharmacists (ASHP) clinical practice guidelines for antimicrobial prophylaxis in surgery, Acnestar Gel, given as an alternative antibiotic in patients with beta-lactam allergy requiring surgical prophylaxis, is effective and recommended for a number of surgical procedures.

Toxoplasma gondii encephalitis and pneumonitis (treatment/long-term maintenance)

Based on the US Department of Health and Human Services guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents and the American Society of Transplantation Infectious Diseases Community of Practice guidelines on parasitic infections in solid organ transplantation, Acnestar Gel (with pyrimethamine and leucovorin) is an effective and recommended alternative regimen for the treatment and long-term maintenance therapy of Toxoplasma gondii encephalitis and pneumonitis.

See also:
What other drugs will affect Acnestar Gel?

With simultaneous use of Acnestar Gel with theophylline, aminophylline, caffeine, there is an increase in their concentration in blood plasma and thus increases the risk of toxic effects.

Erythromycin increases the concentrations of cyclosporine in the blood plasma and may increase the risk of nephrotoxicity.

Drugs that block tubular secretion prolongs T1/2 of erythromycin.

Incompatible with lincomycin, Acnestar Gel and chloramphenicol (antagonism).

Acnestar Gel reduces the bactericidal action of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems).

With simultaneous use of erythromycin increases the concentration of theophylline.

At the same time receiving chemotherapy, which is carried metabolism in the liver (carbamazepine, valproic acid, hexobarbital, phenytoin, alfentanil, dizopiramid, lovastatin, bromocriptine), may increase the concentration of these drugs in plasma (an inhibitor of microsomal liver enzymes).

IV injection of erythromycin increases the effects of ethanol (accelerating gastric emptying and decrease the duration of alcohol dehydrogenase in the gastric mucosa).

Erythromycin reduces the clearance of triazolam and midazolam and therefore may increase the pharmacological effects of benzodiazepines.

At the same time taking with terfenadine or astemizole may develop arrhythmias (fibrillation and ventricular flutter, ventricular tachycardia, until death); with dihydroergotamine or non hydrated ergot alkaloids may vasoconstriction to spasm, dysesthesia.

With simultaneous application Acnestar Gel slows elimination (increases the effect) of methylprednisolone, felodipine and anticoagulants of cumarine series.

In a joint appointment with lovastatin increased rhabdomyolysis.

Erythromycin increases the bioavailability of digoxin.

Erythromycin reduces the effectiveness of hormonal contraceptives.

See also:
What are the possible side effects of Acnestar Gel?

Clinical trials

Non-pregnant Women: In clinical trials involving non-pregnant women, 1.8% of 600 patients who received treatment with Acnestar Gel phosphate vaginal cream 2% for 3 days and 2.7% of 1325 patients who received treatment for 7 days discontinued therapy due to drug-related adverse events. Medical events judged to be related, probably related, possibly related, or of unknown relationship to vaginally administered Acnestar Gel phosphate vaginal cream 2%, were reported for 20.7% of the patients receiving treatment for 3 days and 21.3% of the patients receiving treatment for 7 days. Events occurring in ≥1% of patients receiving Acnestar Gel phosphate vaginal cream 2% are shown in Table 1.

Table 1- Events Occurring in ≥1% of Non-pregnant Patients Receiving Acnestar Gel Phosphate Vaginal Cream 2%

Other events occurring in <1% of the Acnestar Gel vaginal cream 2% groups include:

Urogenital system: vaginal discharge, metrorrhagia, urinary tract infection, endometriosis, menstrual disorder, vaginitis/vaginal infection, and vaginal pain.

Body as a whole: localized abdominal pain, generalized abdominal pain, abdominal cramps, halitosis, headache, bacterial infection, inflammatory swelling, allergic reaction, and fungal infection.

Digestive system: nausea, vomiting, constipation, dyspepsia, flatulence, diarrhea, and gastrointestinal disorder.

Endocrine system: hyperthyroidism.

Central nervous system: dizziness and vertigo.

Respiratory system: epistaxis.

Skin: pruritus (non-application site), moniliasis, rash, maculopapular rash, erythema, and urticaria.

Special senses: taste perversion.

Pregnant Women: In a clinical trial involving pregnant women during the second trimester, 1.7% of 180 patients who received treatment for 7 days discontinued therapy due to drug-related adverse events. Medical events judged to be related, probably related, possibly related, or of unknown relationship to vaginally administered Acnestar Gel phosphate vaginal cream 2%, were reported for 22.8% of pregnant patients. Events occurring in ≥1% of patients receiving either Acnestar Gel phosphate vaginal cream 2% or placebo are shown in Table 2.

Table 2- Events Occurring in ≥1% of Pregnant Patients Receiving Acnestar Gel Phosphate Vaginal Cream 2% or Placebo

Other events occurring in <1% of the Acnestar Gel vaginal cream 2% group include:

Urogenital system: dysuria, metrorrhagia, vaginal pain, and trichomonal vaginitis.

Body as a whole: upper respiratory infection.

Skin: pruritus (topical application site) and erythema.

Other Acnestar Gel formulations:

Acnestar Gel vaginal cream affords minimal peak serum levels and systemic exposure (AUCs) of Acnestar Gel compared to 100 mg oral Acnestar Gel dosing. Although these lower levels of exposure are less likely to produce the common reactions seen with oral Acnestar Gel, the possibility of these and other reactions cannot be excluded presently. Data from well-controlled trials directly comparing Acnestar Gel administered orally to Acnestar Gel administered vaginally are not available.

The following adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of Acnestar Gel:

Gastrointestinal: Abdominal pain, esophagitis, nausea, vomiting, and diarrhea.

Hematopoietic: Transient neutropenia (leukopenia), eosinophilia, agranulocytosis, and thrombocytopenia have been reported. No direct etiologic relationship to concurrent Acnestar Gel therapy could be made in any of these reports.

Hypersensitivity Reactions: Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with Acnestar Gel. A few cases of anaphylactoid reactions have been reported. If a hypersensitivity reaction occurs, the drug should be discontinued.

Liver: Jaundice and abnormalities in liver function tests have been observed during Acnestar Gel therapy.

Musculoskeletal: Rare instances of polyarthritis have been reported.

Renal: Although no direct relationship of Acnestar Gel to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances.

Acnestar Gel is a semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent compound lincomycin.

Acnestar Gel phosphate is a water soluble ester of Acnestar Gel and phosphoric acid.

Acnestar Gel phosphate is L-threo-α-D-galacto-Octopyranoside, methyl 7-chloro-6, 7, 8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl] amino]-1-thio-, 2-(dihydrogen phosphate), (2S-trans)-.

The molecular formula is C₁₈H₃₄CIN₂O₈PS and the molecular weight is 504.96.

Acnestar Gel hydrochloride is the hydrated hydrochloride salt of Acnestar Gel. Acnestar Gel hydrochloride is Methyl 7-chloro-6, 7, 8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside monohydrochloride.

Acnestar Gel palmitate hydrochloride is a water soluble salt of ester of Acnestar Gel and palmitic acid. Acnestar Gel palmitate hydrochloride is Methyl 7-chloro-6, 7, 8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-palmitate monohydrochloride.