Side Effects of Perlane (hyaluronic acid)

Perlane (hyaluronic acid) is a substance normally produced by the body; it is what gives skin its volume and fullness. Perlane is used for treating facial wrinkles and folds. It is classified as a medical device.

When Perlane is injected into wrinkled skin it adds fullness and reduces the prominence of the wrinkles in the previously wrinkled area. Perlane also attracts and binds water, and this also helps maintain fullness in the area of injection. The benefit of Perlane may last for six months or longer. 

Common side effects of Perlane include

• bruising,
• redness,
• pain,
• itching,
• tenderness, and
• swelling.

Serious side effects of Perlane include

• infection,
• allergic reactions,
• death of tissue (necrosis), and
• acne.

Drug interactions of Perlane are not listed in the prescribing information. Perlane is classified as a medical device.

Use of Perlane during pregnancy has not been evaluated. Use of Perlane by nursing mothers has not been evaluated. Consult your doctor before breastfeeding. 

The most common side effects of hyaluronic acid are reactions at the site of injection such as:

• bruising,
• redness,
• pain,
• itching,
• tenderness, and
• swelling.

Vitamin E supplements, St. John's Wort, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) such as Aleve and Motrin may increase bruising or bleeding after injection of hyaluronic acid. Therefore, patients should stop these drugs at least one week before the injections.

Post marketing adverse effects that have been reported include:

• infection,
• allergic
• reactions,
• necrosis (death of tissue), and
• acne.

Adverse Experiences

• In two U.S. studies (i.e., Study MA-1400-01 and Study MA-1400-02) involving 433 patients at 25 centers, the adverse outcomes reported in patient diaries during 14 days after treatment are presented in Tables 1–4.
• The physician diagnosed adverse events identified in these studies at 72 hours after injection are presented in Table 5.
• In Study MA-1400-01, 150 patients were injected with Perlane on one side of the face and Restylane on the other side of the face.
• In study MA-1400-02, 283 patients were randomized to receive either Perlane or Restylane injection on both sides of the face.
• Table 6 presents all investigator identified adverse experiences recorded at study visits 2 weeks or more after injection in studies MA-1400- 01, MA-1400-02, 31GE0101 and 31GE0002.
• In Study 31GE0101, 150 Canadian patients were injected with both Perlane and Hylaform. 
• In Study 31GE0002, 68 Scandinavian patients underwent both Perlane and Zyplast injections.
• Table 5 shows the number of adverse experiences identified by investigators at 72 hours after injection for Studies MA-1400-01 and MA-1400-02. Some patients had multiple adverse experiences or had the same adverse experience at multiple injection sites. No adverse experiences were of severe intensity.
• Table 6 presents the number of patients and per patient incidence of all adverse experiences identified by investigators at visits occurring two or more weeks after injection.
• In two studies (i.e., 31GE0101 and 31GE0002) with repeat administration of Perlane at 6–9 months following the initial correction, the incidence and
• Severity of adverse experiences were similar in nature and duration to those recorded during the initial treatment sessions.
• In all four studies, investigators reported the following local and systemic events that were judged unrelated to treatment and occurred at an incidence of less than 1%, i.e.,
  • acne;
  • tooth disorders (e.g., pain, infection, abscess, fracture);
  • dermatitis (e.g., rosacea, unspecified, contact, impetigo, herpetic);
  • unrelated injection site reactions (e.g., desquamation, rash, anesthesia);
  • facial palsy with co-administration of botulinum toxin;
  • headache/migraine;
  • nausea (with or without vomiting);
  • syncope;
  • gastroenteritis;
  • upper respiratory or influenza-like illness;
  • bronchitis;
  • sinusitis;
  • pharyngitis;
  • otitis;
  • viral infection;
  • cystitis;
  • diverticulitis;
  • injuries;
  • lacerations;
  • back pain;
  • rheumatoid arthritis; and
  • various medical conditions such as chest pain, depression, renal stones, and uterine fibroids.

Post-Marketing Surveillance

The following adverse events were received from post-marketing surveillance for Restylane and Perlane in the U.S. and other countries:

• presumptive bacterial infections,
• inflammatory adverse events,
• necrosis,
• injection site numbness/tingling, and
• vasovagal reactions.

Reported treatments have included

• systemic steroids,
• systemic antibiotics, and
• intravenous administrations of medications.

Additionally, delayed inflammatory reaction to Restylane has been observed with

• swelling,
• redness,
• tenderness,
• induration and
• rarely acneform papules at the injection site with onset as long as several weeks after the initial treatment.

Average duration of these effects is two weeks.

Implant and injection site reactions, mostly non-serious events, have also been reported. These include:

• discoloration,
• bruising,
• swelling,
• mass formation,
• erythema,
• pain,
• scarring and
• ischemia.

Most instances of discoloration including hyperpigmentation, sometimes described as a blue or brown color and ranging from mild to severe, have occurred within the same day as treatment but have also occurred up to 6 months post-treatment. These events typically resolve within a few days but with some infrequent instances lasting up to 18 months. 

• Implant and/or injection site bruising, swelling, erythema and pain generally occurred on the same day as treatment usually resolving within 1 to 4 weeks. Some occurrences have persisted for up to 6 months.
• Severity for these events is generally mild to moderate although some cases have been severe. Mild to moderate mass formations (typically described as lumps or bumps) have also been seen ranging in onset from 1 day to 6 months post implantation.
• Rarely, events of this type have been observed for up to 13 months. These events usually resolved within 1 to 5 months.
• Mild to moderate scarring was rarely observed.
• Onset of symptoms ranged from immediate post-treatment to up to 1 year following implantation. Symptom resolution was approximately 3 weeks with 1 instance lasting up to 3 years.
• Most ischemic events have occurred immediately following implantation and ranged in severity from moderate to severe. Events were resolving as early as 2 days and up to 9 weeks post-treatment.
• Symptoms associated with herpetic eruptions which included swelling, pain, whiteheads, vesicles and erythema have been reported and commonly occurred within 2 days to 1 month following implantation. Severity ranged from mild to moderate and resolution of symptoms ranged from 1 to 15 weeks.
• Telangiectasias and capillary disorders, commonly characterized as broken capillaries, have been reported and occurred with an onset of 1 day to 7 weeks. Most events ranged in severity from mild to moderate with a few severe instances. Duration of events ranged from 2 weeks up to 13 months.
• Very rarely, instances of moderate to severe biopsyconfirmed granuloma were observed. Onset ranged from 3 weeks to 4 months with resolution between 6 weeks to 11 months.
• Events of mild to moderate hypoaesthesia have occurred ranging in onset from 1 day to 1 week. Duration and resolution occurred between 1 day and 10 weeks.
• Serious adverse events have been rarely reported. The most commonly reported serious adverse events (by MedDRA Preferred Term) were
  • hypersensitivity, and implant and/or injection site swelling,
  • ischemia and
  • discoloration.
• Of these infrequently reported serious events, only one adverse event has occurred in a frequency of 5 or greater:
• Hypersensitivity reactions ranging from moderate to severe mostly occurred within 1 to 2 days of implantation and up to 3 weeks. Reported symptoms included
  • swelling;
  • itching on chest and back;
  • puffy, burning, watery, and itchy eyes; and
  • shortness of breath.
• Treatments included
  • steroids,
  • diphenhydramine,
  • unspecified intravenous medication,
  • oxygen and
  • various creams.
• An evaluation of patients who reported potential hypersensitivity reactions did not demonstrate any evidence of IgE or cell mediated immunologic reactions specifically directed at hyaluronic acid. Most hypersensitivity events resolved within 1 to 14 days with or without treatment.

Adverse reactions should be reported to Medicis Aesthetics Inc. at 1-866-222-1480.

No information provided.