TABLE 1.
Summary of Studies with Complications of Facial Fillers
| Author (First Listed), Year | Study Design | No. of Patients (Gender) | Age (Mean) | Geographic Location | Type of Filler | Area of Injection | Timing of Onset | Type of Complication | Therapy (Medical/Surgical) | Outcome | Level of Evidence |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Hönig et al, 20032 | Case report | 1 (F) | 54 | Germany | HA | Nasolabial fold | Several days | Redness and intermittent swelling of the nasolabial folds. Development of palpable and painful erythematous nodular papule-cystic which evolved into severe bilateral abscesses | Drainage of the abscesses; excision of the recurrences of granulomatous allergic tissue reactions; surgical correction of the nasolabial fold | Complete healing without recurrences after surgery | 5 |
| Arron and Neuhaus 200713 | Case report | 1 (F) | 59 | United States | HA (Matridur and Matrigel) | Glabella, nasolabial fold, lips | 2 d; 5 d hospitalization | Facial edema, erythema of the glabella and nasolabial folds and beyond | Azathioprine and methylprednisolone. The patient refused the treatment with hyaluronidase | Signs completely resolved by 1 y after the injections | 5 |
| Sires et al, 200814 | Case report | 1 (F) | 57 | United States | CaHa (Radiesse) | Glabella, nasolabial fold | Immediate | Herpetic appearing skin lesions, tenderness and tingling along with redness and bumps. Vesicles along the ophthalmic branch of the trigeminal nerve | Ciprofloxacin, after 3 d worsening of the lesions. Acyclovir 800 mg 5 times a day for 10 d | After 1-month, complete resolution of the lesions | 5 |
| Kwon et al, 201315 | Case report | 1 (F) | 20 | Korea | HA | Nasal dorsum | Immediate | Ischemic oculomotor nerve palsy and glabellar skin necrosis. Blepharoptosis, strabismus. Intermittent diplopia | Aspirin, nicegorlin, corticosteroids, Epidermal growth factor spray, sodium hyaluronate gel, antibacterial ointment | 6 mo from the event full recovery | 5 |
| Oh et al, 201416 | Case report | 1 (F) | 33 | Korea | HA | Glabella, asal ala | Immediate | Vision loss in the right eye without light perception | 700 units of hyaluronidase and 20,000 units of urokinase into the ophthalmic artery. Next, 800 units of hyaluronidase were infused into the branches of the right ECA | No visual improvement at 1-mo control | 5 |
| Tracy et al, 20144 | Case report | 1 (F) | 41 | United States | CaHa | Nasolabial fold | 1–11 d | Swelling and skin changes to her left alar crease. Later on, necrosis of the injected area due to a local herpes zoster reactivation | Valaciclovir; daily local wound care regimen with daily wound debridement | Acceptable aesthetic result with minimal residual scar | 5 |
| Rongioletti et al, 201417 | Case report | 3 (F) | 61.3 | Italy | HA (n = 3) | Glabella, cheeks, nasolabial fold, perioral (n = 2); Lips (n = 1) | Few months | Firm, nodular swellings involving the facial areas of the injection | Minocycline 200 mg (3 mo) (n = 1). Excision of the granulomas (n = 2) | Slight (n = 1) to good (n = 2) aesthetic result | 4 |
| Hsieh et al, 201518 | Case report | 2 (F) | 40 | Taiwan | CaHa | Glabellar area (n = 2) | Immediate | Central retinal artery occlusion, ophthalmoplegia, glabellar skin necrosis, monolateral blindness (n = 1) Bilateral anterior ischemic optic neuropathy and chorioretinal vascular occlusion over the left eye with visual impairment and visual field defect (n = 1) |
Anterior chamber paracentesis, timolol, acetazolamide, oral antiplatelet, topical betamethasone(n = 1) Hyperbaric oxygen therapy, systemic low-dose steroids, antiaggregant, topical and oral antiglaucomatous agents (n = 1) |
Blindness left eye at the control (n = 1) Altitudinal visual field defects in both eyes and generalized depression in the visual field of the left eye (n = 1) |
4 |
| Sun et al, 201519 | Retrospective review | 20 (F, n = 19; M, n = 1) | 29 | China | HA | Nasal dorsum (n = 15); nasolabial fold (n = 6) | 1 d | Erythema, swelling, skin necrosis (n = 20) | Injection of ovine testicular hyaluronidase in the soft tissues, antibiotics, tanshinone, papaverine, topical magnesium sulphate, infrared irradiation, hyperbaric oxygen | After treatment, 65% (n = 13) recovered fully and the remaining 35% (n = 7) developed full skin necrosis and scar formation | 4 |
| Chou et al, 201520 | Case report | 1 (F) | 35 | Taiwan | CaHa (Radiesse) | Nasal dorsum, nasal tip | Immediate | Choroid vascular occlusion leading to left ischemic optic neuropathy, blurred vision and glabellar skin necrosis | Alprostadil, dextran to improve blood supply; hyperbaric oxygen therapy (10×) | Visual acuity to 6/60 on the left eye after 1 mo | 5 |
| Schuster, 201521 | Retrospective review | 7 (F, n = 6; M, n = 1) | Not reported | Germany | CaHa (n = 7) | Nasal dorsum (n = 6); nasal tip (n = 1) | Not reported | Filler dislocation (n = 1), visible hematoma (n = 2), subcutaneous nodules persisting for up to 8 wks after injection (n = 1), painless red nasal tip (n = 1), local infection at the injection site (n = 1), subdermal abscess with skin necrosis (n = 1) | Topical corticosteroids, systemic antibiotics (n = 3), local antibiotic ointment (n = 1), incision of the abscess (n = 1) | Complete resolution of the symptoms (n = 6); no information on the follow-up (n = 1). | 4 |
| Andre and Haneke, 201622 | Case report | 6 (F) | 37.5 | France, Switzerland | HA (n = 6) (Restylane) | Nasolabial fold (n = 4); nasal tip (n = 1); lips (n = 1) | Immediate | Nicolau Syndrome (immediate pain, livedoid pattern, scabs and skin necrosis) | Hyaluronidase, aspirin, topical antiseptic (n = 6) | Full recovery in few weeks | 4 |
| Fan et al, 201623 | Case report | 2 (F) | 26 | China | HA | Temporal region, lacrimal through, cheeks, nasal dorsum, chin (n = 1); forehead (n = 1) | 2–3 d | Anaphylactic reaction with bilateral edema on upper eyelids and itchy milia pimples around center of the face (n = 1); pronounced redness, ulcer, and pustules in the glabellar region (n = 1) | Loratadine 10 mg tablets to take orally once a day, topical tacrolimus ointment (0.03%) for 5 d (n = 1); dexamethasone 20 mg intravenously, hyperbaric oxygen once a day for 6 sessions, amoxicillin capsules 0.5g 3 times a day, aescuven forte tablets 300 mg twice a day, topical recombinant human epidermal growth factor gel on the lesions for 10 d | Complete resolution in both cases at the control | 4 |
| Kang et al, 201624 | Case report | 1 (F) | 46 | Korea | HA | Glabella, forehead, nasal dorsum | 2 d | Inflammatory symptoms with redness, swelling, numerous pustules, and dark regional necrosis | Hyaluronidase, oral antibiotics, prednisolone 15mg, debridement and injected PRP intradermally and topically with a dressing. After 2 wks additional PRP with topical fucidic acid, carbon dioxide laser for the scar | On the 10th day, the wound was completely re-epithelialized with residual erythema and a depressed scar. After 10 mo the scar had improved with satisfactory results and only a slightly noticeable scar remained | 5 |
| Kim et al, 201622 | Case report | 4 (F) | Not reported | Korea | HA | Glabella; nasolabial fold (n = 4) | Immediate | Unilateral ophthalmoplegia with visual loss, total paralysis of infraduction and adduction (n = 4). Palsy of the superior oblique (n = 3). Limitations in supraduction (n = 2). Limitations in abduction (n = 1) | Intraarterial thrombolysis using hyaluronidase (n = 1) | At 8 mo control all the patients remained without light perception in the involved eye | 4 |
| Cohen et al, 201625 | Case report | 1 (F) | 24 | Israel | CaHa | Nasal dorsum | Immediate | Sudden ocular pain and lowering of visual acuity. At the examination marked periorbital edema and hematoma, ptosis, ocular movements limitation, infero-temporal branch retinal artery occlusion and multiple choroidal emboli | Enoxaparin sodium 60 mg 2xdie for 2 d; acetylsalicylic acid 100 mg/die; amoxicillin/clavulanate 875 mg 2xdie for 7 d and prednisone 60 mg/die gradually tapered down; topical antibiotics ofloxacin 0.3% eye drops and mupirocin ointment to the nose bridge and forehead area for 14 d | 18 mo visual acuity was 20/60, visual field examination was deteriorated in comparison with normal exam | 5 |
| Or et al, 201726 | Retrospective review | 7 (F) | 48.2 | United States | HA (n = 2); CaHa (n = 4) | Lower eyelid region (n = 7) | 12 mo (average) | In the lower eyelid comparison of a xanthelasma-like appear lesions: yellowish, flat, and soft plaques | Steroid injections, 5FU injections, ablative or fractionated CO2 laser, direct excision (n = 5); no treatment (n = 2) | Complete healing | 4 |
| Yu et al, 20171 | Case report | 1 (F) | 54 | United Kingdom | HA (Restylane and Teosyal) | Brow region | 21 mo | Chronic bilateral pitting upper eyelid edema lasting 6 y after multiples injections | Hyaluronidase 120 units, was injected into the subcutaneous brows | Healing within 2 d, 2 y-control without recurrences | 5 |
| Zhu et al, 201727 | Retrospective review | 4 (F) | 27 | China | HA | Nasal dorsum (n = 3); forehead (n = 1) | Immediate | Vision loss (n = 3); blurred vision (n = 1); blepharoptosis (n = 4); ophthalmoplegia with oculomotor nerve palsy (n = 2) | One or two retrobulbar injections of hyaluronidase (1500–3000 U) (n = 4); corticosteroids (n = 3) | No improvement after treatment in all patients | 4 |
| Lee et al, 201728 | Case report | 1 (F) | 25 | Korea | HA (Bellast) | Temporal area | Immediate | Ecchymosis on the left nasal ridge, ptosis of the left eye, a conjunctival injection, a dilated pupil in the left eye, diplopia in all directions | Systemic steroid injections (2 wks), broad-spectrum antibiotics (1 wk). The skin lesion was dressed twice per day with an epidermal growth factor spray and antibacterial ointment |
6 mo control showed improvement of the skin lesion with minimal residual scarring and persistent diplopia | 5 |
| Dagi Glass et al, 201729 | Case report | 1 (F) | 64 | United States | CaHa | Temples, cheeks, forehead, chin | Immediate | Horizontal diplopia and right upper eyelid ptosis | Oral steroids | At 2-mo follow-up, there was moderate clinical improvement | 5 |
| Kim et al, 201730 | Case report | 1 (F) | 41 | Korea | HA | Nasolabial fold | Immediate | Erythema, swelling, tenderness, multiple vesicle formations on the left side of face, skin necrosis in the area where she had a facial injury 8 y before, which potentially compromised her vascular network | Hyaluronidase, aspirin, ciprofloxacin and clarithromycin (10 d), and local bacitracin (16 d) Surgical remove of the wound 13 d after injection |
4 mo-control showed minimal asymmetry of nostrils lied to minimal skin defect in the left nostril and the alar base | 5 |
| Shin et al, 201731 | Case report | 1 (F) | 58 | Korea | HA | Cheeks, chin | 1 mo | Erythematous inflammatory nodules, colture positive to Aspergillus | Incision, drainage of the lesion, colture of the pus Voriconazole injection |
Complete healing | 5 |
| Vu et al, 201832 | Case report | 1 (F) | 51 | United States | CaHa | Glabella, nasal dorsum | Immediate – 1 h | Nausea, vomiting, headache, loss of vision of the right eye; necrosis of skin of the forehead and glabella | Retrobulbar hyaluronidase injection, ocular massage, prednisone and aspirin | One day later, visual acuity improved to light perception that remained stable at 3 mo; glabellar and forehead skin presented erythematous, depressed scars | 5 |
| Vidič and Bartenjev, 201833 | Case report | 1 (F) | 50 | Slovenia | HA | Upper lip, nasal dorsum, glabella, marionettes | 3 d | Erythematous, livedoid rash at the site of the injection in the glabellar region and from the nasal root to the scalp and left upper eyelid | Antibiotic (azithromycin 500 mg) for 6d p.o., corticosteroid (methylprednisolone 32 mg) p.o. for 5 d | 1 mo-control showed complete healing | 5 |
| Khoo et al, 201834 | Case report | 1 (F) | 27 | Malaysia | HA | Nasolabial fold | 1–5 wks | Fever, lethargy, headache. At 5 wks developing of encephalitis positive to HST-1 with altered mental state and seizures | Intubation for the status epilepticus, phenytoin 15 mg/kg, ceftriaxone 2 g and acyclovir 500 mg. After the diagnosis of HSVT-1, acyclovir IV (3 wks) and methylprednisolone (5 d). Levetiracetam for the seizures |
After 2 mo postencephalitic syndrome (hypomania, self-injury, hyperphagia), transfer in psychiatry department. 3 mo follow-up showed poor cognitive functions | 5 |
| Bae et al, 201835 | Case report | 1 (F) | 29 | Korea | HA (Elarvie) | Nasal tip | Immediate – 3 d | Severe pain, dizziness, and blurred vision. Visual disturbance and extraocular movements limitation. Later comparison of violaceous necrotic skin lesions on right periocular and glabellar area | Hyaluronidase subcutaneously, systemic steroid (methylprednisolone), vasodilator (nitroglycerin, alprostadil), prophylactic antibiotics, and daily dressing with LLLT (low-level laser therapy | After 2 wks, skin necrosis and ocular movement are gradually recovered, confirmed at 1-y control | 5 |
| Robati et al, 201836 | Retrospective review | 7 (F) | 33 | Iran | HA | Lips, nasolabial fold (n = 6); nasal dorsum (n = 1) | Immediate – 3 d | Vascular complications leading to severe pain, tenderness, firm swelling, cyanotic discoloration, pustule formation, necrosis | Hyaluronidase (100 to 300 UI) | Reversion of the symptoms | 4 |
| Alshaer et al, 201837 | Case report | 1 (F) | 56 | Saudi Arabia | HA | Cheeks | 17 y | Painful swelling of the right cheek after a failed trial of filler evacuation and intralesional corticosteroid injection. Isolation of Brucella cells at micro bacterial examination | Incision and drainage, colture, cefazolin (1 g every 8 h for 8 d) IV and paracetamol (1 g every 6 h for 2 d). Second incision and drainage, doxycycline 100 mg tablets (every 12 h for 42 d) and streptomycin 1 g IM injection for 14 d | All the symptoms resolved | 5 |
| Fang et al, 201838 | Case report | 1 (F) | 31 | Indonesia | HA (Juvederm) | Chin | Immediate – 2 d | Blanching of skin on the right side of chin and upper neck areas with severe pain in all the chin area and during the swallowing process. Later comparison of livedo reticularis/skin around the blanched skin patch extending from the mental crease to the upper cervical area. Later the development of multiple small pustules | Hyaluronidase 1000 U in the injected area and 1cm above the skin reaction immediately and after 1 h. Oral cefixime 200 mg (2/24H) and acetylsalicylic acid 75 mg (1/24H) and topical mupirocin ointment | After 4 wks all symptoms were gone | 5 |
| Henderson et al, 201839 | Case report | 1 (F) | 37 | United States | HA (Juvederm) | Temples | Immediate | Hearing loss in the left ear without vestibular symptoms, blanching over the left side of the face, severe pain | Immediate hyaluronidase, topical nitro paste, warm compresses. After 9 h enoxaparin, aspirin, dexamethasone 10 mg IV, piperacillin/tazobactam, and intradermal 1% lidocaine (0.1 ml per site) After 15 h hyperbaric oxygen treatments (6 in total, twice a day, the initial 2 at 3.0 atmospheres absolute for 90 min followed by 4 treatments at 2.4 ATA × 90 min) Sessions of PRP for residual erythema after discharge |
After 3 d, hearing back to the baseline subjectively, no hearing test were performed. At 1-y follow-up, complete resolution of the skin lesions |
5 |
| Thanasarnaksorn et al, 201840 | Case report | 6 (F, n = 5; M, n = 1) | 35.5 | Thailand, United States | HA | Nose (n = 4), forehead (n = 1); temple (n = 1) | Immediate | Ophthalmic artery occlusion (n = 2); Central retinal artery occlusion (n = 2) with nerve III palsy (n = 1); right peripheral retinal ischemia and choroidal ischemia (n = 1) | Hyaluronidase, methylprednisolone, antiplatelet drugs, oral antibiotic, antiepileptic drug, topical steroid eye drop, topical antibiotic eye drop, hyperbaric oxygen, anterior chamber paracentesis | Vision loss in the affected eye (n = 2); full recovery (n = 4) | 4 |
| Han et al, 201841 | Case report | 1 (F) | 42 | China | HA | Forehead | 2 d | Necrotic circular skin lesion of approximately 1 cm in the glabellar region with a thin overlaying scab. Persistent tenderness and pain extending from the right glabella to the top of the forehead | Combination of recombinant bovine basic fibroblast growth factor gel and antibiotic ointment | At 14 d-control the wound was re-epithelialized with residual erythema and a depressed scar | 5 |
| Wang et al, 201842 | Case report | 2 (F) | 33 | China | HA | Chin (n = 2) | Immediate – 1 d | Paleness evolved in red-black discoloration with formation of blisters in the anterior region of the chin and necrosis (n = 2) Numbness in the right side of the tongue, neck pain, and headache (n = 1) |
Hyaluronidase, hot compresses and a recombinant human epidermal growth factor gel | Skin necrosis gradually evolved in a superficial ulcer (n = 1) At 9 d-control mild atrophy and paraesthesia of the affected side of the tongue (n = 1) |
4 |
| Doerfler and Hanke, 201943 | Case report | 1 (F) | 34 | United States | HA (Juvederm) | Nasolabial fold | Few hours | Few hours later the injection, discoloration of the skin and tenderness of the nasolabial fold; the day after erythematous plaque with overlying pustules evolving in skin necrosis | Hyaluronidase (300 U) warm compresses, aspirin 80 mg, nitroglycerin ointment, cephalexin 500 mg, valaciclovir 1 g, methylprednisolone, mupirocin ointment, petrolatum | Excellent 7-mo outcome | 5 |
| Chauhan and Singh, 201944 | Case report | 1 (M) | 50 | India | HA | Cheeks, glabella, nasolabial | 2 d | Necrosed micro vesicles in the infraorbital artery territory with signs of impending skin necrosis and redness (livedo reticularis) extending from infraorbital region up to the nasolabial fold | Hyaluronidase (2000 U divided in 4 doses in 1 d) | At the end of 3 mo skin had completely healed without any residual scarring or pigmentation | 5 |
| Zhang et al, 201945 | Retrospective review | 3 (F) | 30 | China | HA | Nasal dorsum (n = 2); glabella (n = 1) | Immediate | Complete visual field loss of the left eye and ophthalmodynia (n = 1); visual defect on the upper side of the right eye, diplopia and limitation of medial motion (n = 1); complete visual field loss and ptosis of the right eye (n = 1) | Hyaluronidase injection in the sites of the filler injections; glucocorticoid; anticoagulant; hyperbaric oxygen (n = 3); hyaluronidase (retrobulbar injection) (n = 1) | No improvement in the visual acuity | 4 |
| Marusza et al, 201946 | Retrospective review | 22 (F) | 47.3 | Poland | HA | Nasolabial fold (n = 7); tear through (n = 6); cheeks (n = 5); corners of mouth (n = 4) | 1–18 mo | Symptoms of late bacterial infection) as induration, swelling, erythema, pain, and loss of function | Netsvyetayeva (M&N) scheme of comprehensive treatment (n = 17): Puncturing the lesion with an 18 G needle, followed by drainage of pus and fermented cross-linked HA twice a week, until complete resolution; Local administration of hyaluronidase directly onto the lesion twice a week for 14–21 d or until complete resolution of swelling and nodules; Moxioxacin 2400 mg and clarithromycin 2500 mg per os for 14–21 d. Probiotic formulation during the antibiotic therapy |
Resolution of local symptoms was achieved after treatment lasting 14–21 d, with no recurrences at 2-mo control After the 2-mo period, all patients underwent remedial therapy with cross-linked HA, with no infectious complications at the site of administration within the subsequent 2 y (n = 17) |
4 |
| Oh et al, 201947 | Case report | 1 (F) | 48 | United States | CaHa (Radiesse) | Glabellar region | Immediate | Vision loss: no light perception OD, and 20/20 OS | No feasible therapy was identified to restore visual function | 9-mo follow-up: no light perception in the right eye with ischemia and fibrosis on examination of the retina | 5 |
| Ciancio et al, 201948 | Case report | 2 (F) | 40.5 | Italy | HA | Nasolabial fold (n = 2) | 3 d | Skin suffering with erythematous and blister formation | Early infiltration of hyaluronidase in the treated areas (40 IU per cm2); acetylsalicylic acid 100 mg/24 h (10 d); prednisone 25 mg/24 h (4 d); levofloxacin 500 mg/24 h (4 d); topical cream with nitric oxide 2 times a day and compresses with gauze and warm | Good outcome; in both cases necrotic complications were avoided | 4 |
| Turkmani et al, 201949 | Retrospective review | 14 (F) | 40.5 | Saudi Arabia | HA (Juvederm, Teosyal, Belotero, Surgiderm, Restylane, Inamed) | Tear through (n = 8), lips (n = 3), cheeks (n = 9) | 2–10 mo | Localized redness and firm, painful swelling at the sites of previously injected fillers. Reactions started 3–5 d after patients had experienced influenza-like illness (fever, headache, sore throat, cough, and fatigue) | Oral prednisolone 20–30 mg or methylprednisolone 16–24 mg daily for 5 d, followed by tempering of the dose for another 5 d. Treatment with local hyaluronidase was needed in 4 patients after 2 wks | Complete resolutions of symptoms | 4 |
| Uittenbogaard et al, 201950 | Case report | 1 (F) | 46 | The Netherlands | CaHa | Temporal area | Immediate – 2 d | Dermal ischemia | Hyaluronidase, warm compresses, sildenafil, prednisolone, nifedipine for a week. Hyperbaric therapy (10×) | Excellent cosmetic outcome at 6-mo follow-up | 5 |
| Khalil et al, 202051 | Case report | 1 (F) | 54 | United States | HA | Brows, glabella | 2 mo | Edema of the upper eyelids, xerophthalmia, and dryness of her nasal mucous membranes | Hyaluronidase (20 U) were injected into the areas of filler placement immediately and after 3 wks (40U) | Almost instantaneous resolution of the edema | 5 |
| Kaczorowski et al, 202052 | Case report | 1 (F) | 52 | Poland | HA | Nasolabial fold, lips | 2 y | Solid, painless mass in the right buccal area interpreted as a delayed granulomatous reaction to HA associated with its migration from the injection site. Differential diagnosis with a malignancy was made | Excision, layer-by-layer suture with a temporary gauze compression was applied for 5 d | Good results; correction with lipotransfer was planned | 5 |
| Halepas et al, 202053 | Case report | 1 (F) | 52 | United States | HA | Marionettes lines, nasolabial folds | 12 h | Erythematous swelling of the facial skin on the left side in the area lateral and inferior to the lower lip | Warm compresses, 600 U of hyaluronidase, aspirin 325 mg, nitroglycerin paste | Day 9 control did not show ocular or facial disturbances | 5 |
| Zhang et al, 202054 | Retrospective review | 24 (F, n = 23; M, n = 1) | 26 | China | HA | Nasal dorsum (n = 12); temporal area (n = 1); forehead (n = 10); glabella (n = 1) | Immediate | Severe decrease in visual acuity or blindness combined with weakness in opening of their eyes, dizziness, nausea, vomiting, severe headache or ocular pain, and skin numbness, ptosis (n = 24); no light perception (n = 19) | Thrombolytic agents, hyaluronidase or hyaluronidase with urokinase were slowly injected into the ophthalmic artery, mechanical recanalization with micro guidewire (n = 24). Retrobulbar injection of tobramycin 20 mg and dexamethasone 2.5 mg; prednisolone acetate ophthalmic suspension eye drops, levofloxacin, sodium hyaluronate eye drops, and deproteinized calf blood extract eye gel | Only 42% (n = 10) of patients had improvements to visual acuity. The best treatment protocol was the hyaluronidase combined with urokinase. Facial skin necrosis restored to nearly normal appearance (n = 24). | 4 |
| Total articles: 46 | Case report: 37 Retrospective review: 9 |
Total patients: 164 (F, n = 159; M, n = 5) | Mean age: 41.4 |
F, female patients; IM, intramuscle; M, male patients; IV, intravenous; p.o., per os.