Acne Ultra Gel

Pregnancy & Breastfeeding:

Clindamycin Phosphate:

Generally considered safe in topical form, but oral
use requires caution.
Niacinamide: Safe during pregnancy and breastfeeding.
Tretinoin: Avoided during pregnancy due to high risks of birth defects.
Topical use during breastfeeding is typically considered safe but should be
approached with caution.

Clindamycin Phosphate

• Mechanism of Action: Clindamycin binds to the 23S RNA of the 50S ribosomal subunit of bacteria, inhibiting protein synthesis. This makes it bacteriostatic, meaning it stops bacterial growth rather than killing bacteria directly. It is effective against anaerobic bacteria and some Gram-positive cocci. The exact mechanism by which clindamycin treats acne vulgaris is not well understood.
• Resistance: Resistance is often due to modification of the 23S ribosomal RNA. Clindamycin shares cross-resistance with lincomycin and sometimes with macrolides and streptogramin B due to overlapping binding sites. Inducible resistance can occur in macrolide-resistant strains, so these strains should be screened for clindamycin resistance.
• Adverse Effects: Clindamycin can cause pseudomembranous colitis due to Clostridium difficile overgrowth. Resistance has been noted in some strains, such as Clostridium perfringens and Bacteroides fragilis, with resistance potentially persisting for some time after treatment.

Niacinamide

• Mechanism of Action: Niacinamide acts as a precursor to the coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate), which are involved in over 200 redox reactions in cellular metabolism. These coenzymes play a role in glucose metabolism, fat and protein conversion, and other cellular processes. Unlike nicotinic acid, niacinamide does not induce flushing and does not have lipid-altering effects.
• Pharmacologic Effects: Niacinamide is used in acne treatments due to its anti-inflammatory properties and ability to improve skin barrier function. It does not have the hypolipidemic effects of nicotinic acid (niacin), which is used to lower cholesterol levels.

Tretinoin

• Mechanism of Action: Tretinoin, a retinoid, binds to retinoic acid receptors (RARs) rather than retinoid X receptors (RXRs). It affects cellular differentiation, proliferation, and apoptosis. By binding to RARs, tretinoin modifies gene expression, protein synthesis, and epithelial cell growth. It increases epidermal cell turnover and reduces comedone formation, which helps in treating acne.
• Photodamage: Tretinoin inhibits metalloproteinases (enzymes that degrade collagen) induced by UV irradiation, thus reducing fine wrinkles, hyperpigmentation, and roughness associated with sun damage.
• Acute Promyelocytic Leukemia (APL): Tretinoin promotes differentiation of APL cells by converting the inhibitory effects of the PML-RAR-alpha fusion protein into stimulatory effects, leading to terminal differentiation of the malignant cells.

Clindamycin Phosphate

• Contraindications:
• Hypersensitivity: Contraindicated in individuals with known hypersensitivity to clindamycin or lincomycin due to potential cross-sensitivity.
• History of Severe Reactions: Use is contraindicated in patients with a history of severe skin or hypersensitivity reactions.
• Pseudomembranous Colitis: Contraindicated in patients with a history of local enteritis, ulcerative colitis, or pseudomembranous colitis. Topical and vaginal forms are also contraindicated in these cases.
• Precautions:
• Asthma and Allergies: Use with caution in patients with asthma or significant history of hypersensitivity.
• Superinfection Risk: Clindamycin can lead to overgrowth of nonsusceptible organisms, including yeast and fungi. Monitor for signs of superinfection.
• Antibiotic-Associated Colitis: Risk of Clostridium difficile-associated colitis is high. Monitor patients, especially if diarrhea develops during treatment, and consider the possibility of colitis up to 2 months post-treatment.
• Ocular Exposure: Avoid contact with eyes; rinse thoroughly if accidental exposure occurs.
• STDs Screening: Test patients for other STDs if clindamycin is used for sexually transmitted infections.
• Geriatric Use: Increased risk of antibiotic-associated colitis in older adults. Monitor for diarrhea and other side effects closely.
• Long-Term Care Facilities: Follow OBRA guidelines for antibiotic use to prevent secondary infections and monitor for adverse effects.

Niacinamide

• Contraindications:
• Hypersensitivity: Contraindicated in patients with known hypersensitivity to niacin or any component of the formulation.
• Hepatic Disease: Contraindicated in patients with significant or unexplained hepatic disease.
• Precautions:
• Hepatic Monitoring: Monitor liver function tests (LFTs) regularly, particularly with sustained-release formulations, to avoid hepatotoxicity.
• Peptic Ulcer Disease: Contraindicated in patients with active peptic ulcer disease. Use with caution in those with a history of PUD.
• Hypotension and Cardiovascular Conditions: Use cautiously in patients with uncorrected hypotension, acute myocardial infarction, or unstable angina, especially if using other vasodilators.
• Gout and Hyperuricemia: Caution in patients with gout or predisposed to gout due to potential for hyperuricemia.
• Hypophosphatemia: Monitor phosphorus levels periodically, especially in high-dose therapy.
• Diabetes: Use cautiously in diabetic patients due to the risk of hyperglycemia and potential for false-positive glucose test results.
• Pediatric Use: Safety for dyslipidemia in children under 16 is not well-established. Use under specialist guidance if necessary.

Tretinoin

• Contraindications:
• Retinoid Hypersensitivity: Contraindicated in patients with known hypersensitivity to retinoids or vitamin A.
• Fish Allergy: Use caution with formulations containing fish proteins in patients with fish hypersensitivity.
• Eczema: Avoid use in patients with eczema due to potential severe irritation.
• Pregnancy and Nursing: Use during pregnancy or lactation should be limited to the recommended daily allowance. High-dose use is not recommended due to potential risks.
• Precautions:
• Acute Promyelocytic Leukemia (APL) Differentiation Syndrome: Monitor for signs of APL differentiation syndrome, and initiate high-dose steroids if necessary.
• Photosensitivity: Avoid sun exposure and use sunscreen to prevent exacerbation of skin irritation.
• Skin Irritation: Delay use until sunburned skin is healed. Protect treated areas from extreme weather conditions.
• Pediatric Use: Safety and efficacy in children under 12 are not well-established. Oral tretinoin use in infants may require additional monitoring for side effects.
• Ocular Exposure: Avoid contact with eyes and mucous membranes. Rinse thoroughly if contact occurs.
• Flammability: Topical tretinoin is flammable. Avoid use near heat, open flames, or while smoking.

Clindamycin Phosphate

• Gastrointestinal Effects:
• Systemic Therapy: Diarrhea (up to 20%), nausea, vomiting, abdominal pain, constipation (2% or less), esophagitis.
• Topical/Vaginal Preparations: Diarrhea (<1%), stomach cramps, nausea, vomiting, flatulence, dyspepsia, constipation (2% or less), esophagitis.
• Serious Conditions:
• Pseudomembranous Colitis: Clostridium difficile-associated diarrhea (0.01% to 10%); can occur during or after treatment.
• Severe Skin Reactions: Toxic epidermal necrolysis, Stevens-Johnson syndrome; hypersensitivity reactions, urticaria, rash, angioedema, and exfoliative dermatitis.
• Hematologic Effects:
• Neutropenia, eosinophilia, agranulocytosis, thrombocytopenia (rare).
• Other Reactions:
• Topical: Burning, dryness, redness, oiliness, peeling, folliculitis.
• Vaginal: Vaginal pain, inflammation, discharge, bleeding, vulvovaginitis, menstrual disorders.
• Systemic: Jaundice, elevated hepatic enzymes, headache, dizziness, back pain, vertigo, polyarthritis.
• Injection Site: Pain, induration, sterile abscess, thrombo-phlebitis.
• Additional Notes: Rare anaphylactoid reactions, potential for fungal infections, and superinfection.

Niacinamide (Niacin)

• Common Adverse Effects:
• Flushing: Warmth, burning, tingling, especially in the face, neck, and chest. Can cause hypotension, dizziness, and headache.
• GI Effects: Nausea, vomiting, diarrhea, abdominal pain, bloating, dyspepsia. Flushing and GI symptoms more common with immediate-release forms.
• Serious Conditions:
• Liver Issues: Elevated hepatic enzymes, jaundice, potential for fulminant hepatic necrosis with sustained-release forms.
• Glucose Metabolism: Hyperglycemia and exacerbation of diabetes.
• Hyperuricemia: Risk of gout.
• Hypophosphatemia: Monitor serum phosphorus levels.
• Platelet and Coagulation Effects: Slight decreases in platelets, increased prothrombin times.
• Muscle Effects: Rhabdomyolysis (rare with high doses, especially when used with statins).
• Other Reactions:
• Skin: Rash, hyperpigmentation, xerosis.
• Ophthalmic: Blurred vision, macular edema.
• Miscellaneous: Asthenia, insomnia, paresthesias, increased cough.

Tretinoin

• Topical:
• Common: Peeling, dryness, burning, stinging, erythema, pruritus. Severe reactions may require discontinuation.
• Rare: Skin hyperpigmentation, hypopigmentation, increased photosensitivity.
• Oral:
• Common: Dry skin/mucous membranes, rash, pruritus, alopecia, unspecified skin changes.
• Rare: Erythema nodosum, Sweet’s syndrome.
• General Notes:
• Photosensitivity: Increased during both topical and oral use; sunscreen and protective clothing recommended.
• Discontinuation: Severe reactions require stopping therapy and potentially resuming with adjustments.

Clindamycin Phosphate

• Pregnancy:
• Systemic Use: No major congenital abnormalities linked to systemic clindamycin in the second or third trimester, but increased risk of major malformations when used in the first trimester. Clindamycin exposure is associated with musculoskeletal malformations and ventricular/atrial septal defects.
• Vaginal Use: Studies show mixed results. Some trials showed a reduction in preterm birth, while others indicated adverse outcomes such as low birthweight and premature delivery.
• Precautions: Use in the first trimester only if absolutely necessary. Monitor carefully for adverse events.
• Breastfeeding:
• Excretion: Clindamycin is excreted into breast milk at low concentrations.
• Risks: Potential gastrointestinal adverse reactions in the infant. Consider alternative medications if possible. If used, monitor the infant for gastrointestinal issues such as diarrhea and candidiasis.

Niacinamide (Niacin)

• Pregnancy:
• RDA Dosages: Generally considered safe at RDA levels (Pregnancy Category A).
• High Doses: Category C for higher doses. Risks not well-studied, so high doses should be used with caution and only if benefits outweigh potential risks.
• Breastfeeding:
• Excretion: Niacinamide is excreted into breast milk in proportion to maternal intake.
• Recommendations: For lipid-altering doses, discontinuation of breastfeeding may be recommended. Consider the benefits of breastfeeding and potential risks of drug exposure.

Tretinoin

• Pregnancy:
• Teratogenic Effects: High risk of birth defects with oral tretinoin. Topical tretinoin has been associated with animal teratogenic effects, and caution is advised.
• Precautions: Use oral tretinoin only if absolutely necessary and ensure effective contraception. Monthly pregnancy testing and counseling are recommended.
• Breastfeeding:
• Excretion: Unknown if tretinoin is excreted into breast milk. Topical use is less likely to result in significant exposure, but caution is still advised.
• Recommendations: Discontinue breastfeeding before using oral tretinoin. For topical use, consider alternative agents if possible and monitor the infant for any adverse effects.