Veltin Gel

Veltin Gel, containing clindamycin phosphate 1.2% and tretinoin 0.025%, is a yellow, opaque topical gel. Each gram of Veltin Gel contains, as dispensed, 10 mg (1%) clindamycin as clindamycin phosphate, and 0.25 mg (0.025%) tretinoin solubilized in an aqueous-based gel.

Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety data reflect exposure to Veltin Gel in 1,104 subjects with acne vulgaris. Subjects were 12 years and older and were treated once daily in the evening for 12 weeks. Adverse reactions that were reported in ≥1% of subjects treated with Veltin Gel are presented in Table 1.

Table 1. Treatment-Related Adverse Reactions Reported by ≥1% of Subjects

	Veltin Gel N = 1,104 n (%)	Clindamycin Gel N = 1,091 n (%)	Tretinoin Gel N = 1,084 n (%)	Vehicle Gel N = 552 n (%)
Patients with at least one adverse reaction	140 (13)	38 (3)	141 (13)	17 (3)
Application site dryness	64 (6)	12 (1)	62 (6)	3 (1)
Application site irritation	50 (5)	4 (<1)	57 (5)	5 (1)
Application site exfoliation	50 (5)	2 (<1)	56 (5)	2 (<1)
Application site erythema	40 (4)	6 (1)	39 (4)	3 (1)
Application site pruritus	26 (2)	7 (1)	23 (2)	6 (1)
Sunburn	11 (1)	6 (1)	7 (1)	3 (1)
Application site dermatitis	6 (1)	0 (0)	8 (1)	1 (<1)

Local skin reactions actively assessed at baseline and end of treatment with a score >0 are presented in Table 2.

Table 2. Local Skin Reactions in Subjects Treated With Veltin Gel

	Veltin Gel		Vehicle Gel
Local Reaction	Baseline N = 476 (%)	End of Treatment N = 409 (%)	Baseline N = 219 (%)	End of Treatment N = 209 (%)
Erythema	24%	21%	31%	35%
Scaling	8%	19%	14%	12%
Dryness	11%	22%	18%	13%
Burning	8%	13%	8%	4%
Itching	17%	15%	22%	14%

During the 12 weeks of treatment, each local skin reaction peaked at Week 2 and gradually reduced thereafter.

VELTIN (clindamycin phosphate and tretinoin) Gel, 1.2%/0.025%, is a fixed combination of 2 solubilized active ingredients in an aqueous-based gel. Clindamycin phosphate is a water soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin.

The chemical name for clindamycin phosphate 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-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:

Molecular Formula: C18H34ClN2O8PS

Molecular Weight: 504.97

The chemical name for tretinoin is all-trans 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid. It is a member of the retinoid family of compounds.

The structural formula for tretinoin is represented below:

Molecular Formula: C20H28O2

Molecular Weight: 300.44

Veltin Gel contains the following inactive ingredients: anhydrous citric acid, butylated hydroxytoluene, carbomer homopolymer (type C), edetate disodium, laureth 4, methylparaben, propylene glycol, purified water, and tromethamine.

Mechanism of Action

  Clindamycin:[See Microbiology (12.4).]   Tretinoin: Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of folliculare epithelial cells with decreased microcomedone formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.

Pharmacokinetics

In an open-label trial of 17 subjects with moderate-to-severe acne vulgaris, topical administration of approximately 3 grams of Veltin Gel once daily for 5 days, clindamycin concentrations were quantifiable in all 17 subjects starting from 1 hour post-dose. All plasma clindamycin concentrations were ≤5.56 ng/mL on Day 5, with the exception of 1 subject who had a maximum clindamycin concentration of 8.73 ng/mL at 4 hours post-dose. There was no appreciable increase in systemic exposure to tretinoin, as compared with the baseline value. The average tretinoin concentration across all sampling times on Day 5 ranged from 1.19 to 1.23 ng/mL compared with the corresponding baseline mean tretinoin concentration range of 1.16 to 1.30 ng/mL.

Microbiology

No microbiology studies were conducted in the clinical trials with this product.

  Mechanism of Action: Clindamycin binds to the 50S ribosomal subunit of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes (P. acnes), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical trials with Veltin Gel. P. acnes resistance to clindamycin has been documented.   Inducible Clindamycin Resistance: The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g., Staphylococcus aureus, Streptococcus pyogenes). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing.   Cross Resistance: Resistance to clindamycin is often associated with resistance to erythromycin.